Lovastatin inhibits the extracellular-signal-regulated kinase pathway in immortalized rat brain neuroblasts
We have shown previously that lovastatin, a 3-hydroxy-3-methyl- glutaryl coenzyme A reductase inhibitor, induces apoptosis in spontaneously immortalized rat brain neuroblasts. In the present study, we analysed the intracellular signal transduction pathways by which lovastatin induces neuroblast apop...
Saved in:
Published in | Biochemical journal Vol. 401; no. 1; pp. 175 - 183 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Portland Press
01.01.2007
Portland Press Ltd |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | We have shown previously that lovastatin, a 3-hydroxy-3-methyl- glutaryl coenzyme A reductase inhibitor, induces apoptosis in spontaneously immortalized rat brain neuroblasts. In the present study, we analysed the intracellular signal transduction pathways by which lovastatin induces neuroblast apoptosis. We showed that lovastatin efficiently inhibited Ras activation, which was associated with a significant decrease in ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Lovastatin also decreased CREB phosphorylation and CREB-mediated gene expression. The effects of lovastatin on the Ras/ERK1/2/CREB pathway were time- and concentration-dependent and fully prevented by mevalonate. In addition, we showed that two MEK [MAPK (mitogen-activated protein kinase)/ERK kinase] inhibitors, PD98059 and PD184352, were poor inducers of apoptosis in serum-treated neuroblasts. However, these inhibitors significantly increased apoptosis induced by lovastatin treatment. Furthermore, we showed that pharmacological inhibition of both MEK and phosphoinositide 3-kinase activities was able to induce neuroblast apoptosis with similar efficacy as lovastatin. Our results suggest that lovastatin triggers neuroblast apoptosis by regulating several signalling pathways, including the Ras/ERK1/2 pathway. These findings might also contribute to elucidate the intracellular mechanisms involved in the central nervous system side effects associated with statin therapy. |
---|---|
AbstractList | We have shown previously that lovastatin, a 3-hydroxy-3-methyl- glutaryl coenzyme A reductase inhibitor, induces apoptosis in spontaneously immortalized rat brain neuroblasts. In the present study, we analysed the intracellular signal transduction pathways by which lovastatin induces neuroblast apoptosis. We showed that lovastatin efficiently inhibited Ras activation, which was associ-ated with a significant decrease in ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Lovastatin also decreased CREB phosphorylation and CREB-mediated gene expression. The effects of lovastatin on the Ras/ERK1/2/CREB pathway were time- and concentration-dependent and fully prevented by meva-lonate. In addition, we showed that two MEK [MAPK (mitogen-activated protein kinase)/ERK kinase] inhibitors, PD98059 and PD184352, were poor inducers of apoptosis in serum-treated neuroblasts. However, these inhibitors significantly increased apop-tosis induced by lovastatin treatment. Furthermore, we showed that pharmacological inhibition of both MEK and phosphoinos-itide 3-kinase activities was able to induce neuroblast apoptosis with similar efficacy as lovastatin. Our results suggest that lovast-atin triggers neuroblast apoptosis by regulating several signalling pathways, including the Ras/ERK1/2 pathway. These findings might also contribute to elucidate the intracellular mechanisms involved in the central nervous system side effects associated with statin therapy. We have previously shown that lovastatin, an HMG-CoA reductase inhibitor, induces apoptosis in spontaneously immortalized rat brain neuroblasts. In the present study, we analyzed the intracellular signal transduction pathways by which lovastatin induces neuroblast apoptosis. We showed that lovastatin efficiently inhibited Ras activation which was associated with a significant decrease in ERK1/2 phosphorylation. Lovastatin also decreased CREB phosphorylation and CREB-mediated gene expression. The effects of lovastatin on the Ras/ERK1/2/CREB pathway were time- and concentration dependent and fully prevented by mevalonate. In addition, we showed that two MEK inhibitors, PD98059 and PD184352, were poor inducers of apoptosis in serum-treated neuroblasts. However, these inhibitors significantly increased apoptosis induced by lovastatin treatment. Furthermore, we showed that pharmacological inhibition of both MEK and PI3K activities was able to induce neuroblast apoptosis with similar efficacy as lovastatin. Our results suggest that lovastatin triggers neuroblast apoptosis by regulating several signalling pathways, including the Ras/ERK1/2 pathway. These findings might also contribute to elucidate the intracellular mechanisms involved in the central nervous system side effects associated with statin therapy. We have shown previously that lovastatin, a 3-hydroxy-3-methyl- glutaryl coenzyme A reductase inhibitor, induces apoptosis in spontaneously immortalized rat brain neuroblasts. In the present study, we analysed the intracellular signal transduction pathways by which lovastatin induces neuroblast apoptosis. We showed that lovastatin efficiently inhibited Ras activation, which was associated with a significant decrease in ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Lovastatin also decreased CREB phosphorylation and CREB-mediated gene expression. The effects of lovastatin on the Ras/ERK1/2/CREB pathway were time- and concentration-dependent and fully prevented by mevalonate. In addition, we showed that two MEK [MAPK (mitogen-activated protein kinase)/ERK kinase] inhibitors, PD98059 and PD184352, were poor inducers of apoptosis in serum-treated neuroblasts. However, these inhibitors significantly increased apoptosis induced by lovastatin treatment. Furthermore, we showed that pharmacological inhibition of both MEK and phosphoinositide 3-kinase activities was able to induce neuroblast apoptosis with similar efficacy as lovastatin. Our results suggest that lovastatin triggers neuroblast apoptosis by regulating several signalling pathways, including the Ras/ERK1/2 pathway. These findings might also contribute to elucidate the intracellular mechanisms involved in the central nervous system side effects associated with statin therapy. |
Author | Cerezo-Guisado, Maria Isabel García-Marín, Luis Jesús Lorenzo, Maria Jesús García-Román, Natalia Alvarez-Barrientos, Alberto Bragado, Maria Julia |
Author_xml | – sequence: 1 givenname: Maria Isabel surname: Cerezo-Guisado fullname: Cerezo-Guisado, Maria Isabel organization: Departamento de Bioquímica, Biología Molecular y Genética Universidad de Extremadura, E-10071 Cáceres, Spain – sequence: 2 givenname: Natalia surname: García-Román fullname: García-Román, Natalia – sequence: 3 givenname: Luis Jesús surname: García-Marín fullname: García-Marín, Luis Jesús – sequence: 4 givenname: Alberto surname: Alvarez-Barrientos fullname: Alvarez-Barrientos, Alberto – sequence: 5 givenname: Maria Julia surname: Bragado fullname: Bragado, Maria Julia – sequence: 6 givenname: Maria Jesús surname: Lorenzo fullname: Lorenzo, Maria Jesús |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16952276$$D View this record in MEDLINE/PubMed https://hal.science/hal-00478598$$DView record in HAL |
BookMark | eNqFkU1v1DAQhi1URLeFCz8A5YQEUmDsOE58QWor6IdW4gJny0nGG9PEWWxnofx6HO2qLVx6sjzzzDsf7wk5cpNDQl5T-ECBs4_nNwxAQFXQZ2RFeQV5XbH6iKyACZ4LYPSYnITwA4By4PCCHFMhS8YqsSK362mnQ9TRusy63jY2hiz2mOHv6HWLwzAP2ufBbpweco-b9I3YZbfW6YDZVsf-l77LlupxnHzUg_2T0l7HrPE6hR3OfmqG1CO8JM-NHgK-Oryn5PuXz98urvL118vri7N13nJOYy6hZWUrq442uihpTYXpShTUGMEY1qxDQAaGdiiZlpQ2xjSdkahFXbCmwuKUfNrrbudmxK5Fl1YZ1NbbUfs7NWmr_s0426vNtFPpLLWoeRJ4txfo_yu7OlurJQbAq7qU9Y4m9u2hmZ9-zhiiGm1Y7qYdTnNQaSjBZMGfBKkUhQSxKL7fg62fQvBo7kegoBbD1YPhCX7zeNcH9OBw8ReArKqY |
CitedBy_id | crossref_primary_10_1186_s12885_021_08402_6 crossref_primary_10_1080_13543776_2016_1216977 crossref_primary_10_1093_hmg_ddr310 crossref_primary_10_2174_1570159X15666170703101816 crossref_primary_10_1007_s40263_013_0135_1 crossref_primary_10_1007_s13311_021_01082_x crossref_primary_10_1016_j_neubiorev_2021_10_009 crossref_primary_10_1016_j_phrs_2011_04_007 crossref_primary_10_1002_med_20162 crossref_primary_10_1128_MCB_00989_10 crossref_primary_10_1124_pr_111_004994 crossref_primary_10_3109_1354750X_2016_1160289 crossref_primary_10_1016_j_cobeha_2015_01_003 crossref_primary_10_1371_journal_pone_0015697 crossref_primary_10_3389_fpsyt_2021_754485 crossref_primary_10_1002_art_27433 crossref_primary_10_1002_jcb_25579 crossref_primary_10_1016_j_phrs_2014_03_001 crossref_primary_10_1016_j_neurobiolaging_2008_09_004 crossref_primary_10_1016_j_ejps_2010_05_021 crossref_primary_10_1016_j_bcp_2013_10_030 crossref_primary_10_1016_j_pnpbp_2015_11_013 crossref_primary_10_1016_j_neuroscience_2010_02_054 crossref_primary_10_1016_j_phymed_2019_152873 crossref_primary_10_1371_journal_pone_0098080 crossref_primary_10_1186_s11689_017_9186_9 crossref_primary_10_3390_cancers15205100 crossref_primary_10_1186_1756_9966_30_74 crossref_primary_10_1002_jbmr_42 crossref_primary_10_1007_s40265_016_0542_y crossref_primary_10_1002_ajmg_a_36750 crossref_primary_10_1111_j_1471_4159_2008_05458_x crossref_primary_10_3389_fpsyt_2021_762967 crossref_primary_10_1139_y2012_072 crossref_primary_10_1371_journal_pone_0093223 |
Cites_doi | 10.1016/S0014-5793(98)01320-9 10.1126/science.286.5443.1358 10.1111/j.1471-4159.1979.tb11712.x 10.1042/bj3180729 10.1016/S0166-2236(99)01500-3 10.1016/j.atherosclerosis.2004.04.017 10.1016/S1054-8807(03)00104-2 10.1172/JCI109938 10.1023/A:1014588214966 10.1056/NEJM200404083501524 10.1006/mcne.2000.0904 10.1002/cyto.990130802 10.1016/j.nbd.2004.03.013 10.1210/jcem.82.5.3960 10.1111/j.1432-1033.2004.04133.x 10.1016/S0002-9343(01)00870-1 10.1046/j.1440-1681.2002.03711.x 10.1038/343425a0 10.1016/j.neulet.2004.08.020 10.1523/JNEUROSCI.20-08-02852.2000 10.1126/science.270.5240.1326 10.1016/S0022-2275(20)37999-2 10.1016/S0002-8703(00)90033-4 10.1111/j.1471-4159.2005.03345.x 10.1126/science.286.5448.2358 10.1046/j.1471-4159.1999.0722278.x 10.1007/s11010-005-3086-0 10.1016/S0006-2952(02)01388-6 10.1016/S0006-291X(03)00454-6 10.1158/0008-5472.CAN-04-0866 10.1083/jcb.121.2.423 10.1002/ajmg.a.30386 10.1016/S0006-2952(03)00255-7 10.1046/j.1471-4159.2003.02305.x 10.1016/j.cub.2005.07.010 10.1016/j.tcb.2004.09.014 10.1074/jbc.M202245200 10.4049/jimmunol.131.5.2362 10.1078/0171-9335-00155 10.1016/j.ctrv.2004.06.010 10.4049/jimmunol.161.12.6733 10.1016/S0167-4889(99)00007-5 10.1146/annurev.bi.65.070196.001325 10.1016/S0006-2952(03)00075-3 10.1016/S0021-9150(01)00613-X |
ContentType | Journal Article |
Copyright | Distributed under a Creative Commons Attribution 4.0 International License The Biochemical Society, London 2007 |
Copyright_xml | – notice: Distributed under a Creative Commons Attribution 4.0 International License – notice: The Biochemical Society, London 2007 |
DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION 7TK 7X8 1XC VOOES 5PM |
DOI | 10.1042/BJ20060731 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef Neurosciences Abstracts MEDLINE - Academic Hyper Article en Ligne (HAL) Hyper Article en Ligne (HAL) (Open Access) PubMed Central (Full Participant titles) |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef Neurosciences Abstracts MEDLINE - Academic |
DatabaseTitleList | MEDLINE - Academic CrossRef Neurosciences Abstracts MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Anatomy & Physiology Chemistry |
DocumentTitleAlternate | ERK inhibition in lovastatin-induced neuronal apoptosis |
EISSN | 1470-8728 |
EndPage | 183 |
ExternalDocumentID | oai_HAL_hal_00478598v1 10_1042_BJ20060731 16952276 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GroupedDBID | --- -DZ -~X 0R~ 23N 2WC 3EH 3O- 4.4 53G 5GY 5RE 5VS 6J9 79B AABGO AAHRG ABPPZ ABRJW ABTAH ACGFO ACGFS ACNCT ADBBV AEGXH AENEX AI. AIAGR AIZAD ALMA_UNASSIGNED_HOLDINGS BAWUL CGR CS3 CUY CVF DU5 E3Z EBS ECM EIF EJD F5P H13 HH6 HYE HZ~ K-O L7B MV1 MVM N9A NPM O9- OHT OK1 P2P RHI RNS RPM RPO TR2 TWZ VH1 WH7 WOQ XSW Y6R YNY ZY4 ~02 ~KM AAYXX CITATION 7TK 7X8 .55 .GJ 1XC F20 VOOES X7M ZXP 5PM |
ID | FETCH-LOGICAL-c441t-90c25c97d1ba351816fd5e61ff622e82de0e20f1de92a911bffbdf9ea6832b7e3 |
IEDL.DBID | RPM |
ISSN | 0264-6021 |
IngestDate | Tue Sep 17 20:51:49 EDT 2024 Tue Oct 15 15:17:19 EDT 2024 Sat Aug 17 01:33:50 EDT 2024 Sun Sep 29 07:50:43 EDT 2024 Fri Aug 23 01:25:36 EDT 2024 Sat Sep 28 07:50:41 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 1 |
Keywords | Life Sciences |
Language | English |
License | Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0 |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c441t-90c25c97d1ba351816fd5e61ff622e82de0e20f1de92a911bffbdf9ea6832b7e3 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
OpenAccessLink | https://hal.science/hal-00478598 |
PMID | 16952276 |
PQID | 19639061 |
PQPubID | 23462 |
PageCount | 9 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_1698684 hal_primary_oai_HAL_hal_00478598v1 proquest_miscellaneous_68362934 proquest_miscellaneous_19639061 crossref_primary_10_1042_BJ20060731 pubmed_primary_16952276 |
PublicationCentury | 2000 |
PublicationDate | 2007-01-01 |
PublicationDateYYYYMMDD | 2007-01-01 |
PublicationDate_xml | – month: 01 year: 2007 text: 2007-01-01 day: 01 |
PublicationDecade | 2000 |
PublicationPlace | England |
PublicationPlace_xml | – name: England |
PublicationTitle | Biochemical journal |
PublicationTitleAlternate | Biochem J |
PublicationYear | 2007 |
Publisher | Portland Press Portland Press Ltd |
Publisher_xml | – name: Portland Press – name: Portland Press Ltd |
References | 9827563 - FEBS Lett. 1998 Nov 6;438(3):289-92 15030386 - J Neurochem. 2004 Apr;89(1):24-32 11995814 - J Neurooncol. 2002 Jan;56(2):133-42 12694870 - Biochem Pharmacol. 2003 Apr 15;65(8):1295-303 9862703 - J Immunol. 1998 Dec 15;161(12):6733-44 15071140 - N Engl J Med. 2004 Apr 8;350(15):1579-82 12151388 - J Biol Chem. 2002 Oct 4;277(40):37929-35 11882313 - Atherosclerosis. 2002 Mar;161(1):17-26 10652539 - Trends Neurosci. 2000 Feb;23(2):48-53 11583643 - Am J Med. 2001 Oct 1;111(5):390-400 10558990 - Science. 1999 Nov 12;286(5443):1358-62 10740137 - Am Heart J. 2000 Apr;139(4):577-83 10751437 - J Neurosci. 2000 Apr 15;20(8):2852-9 15193300 - Neurobiol Dis. 2004 Jul;16(2):440-53 11322384 - Eur J Cell Biol. 2001 Mar;80(3):207-12 14761784 - Cardiovasc Pathol. 2004 Jan-Feb;13(1):41-8 8385673 - J Cell Biol. 1993 Apr;121(2):423-38 15531395 - Cancer Treat Rev. 2004 Nov;30(7):609-41 7653550 - Am J Physiol. 1995 Aug;269(2 Pt 1):E331-40 15262179 - Atherosclerosis. 2004 Aug;175(2):235-43 8836113 - Biochem J. 1996 Sep 15;318 ( Pt 3):729-47 15786722 - Mol Cell Biochem. 2005 Jan;269(1-2):109-14 10600750 - Science. 1999 Dec 17;286(5448):2358-61 15488325 - Neurosci Lett. 2004 Nov 11;370(2-3):212-7 12907245 - Biochem Pharmacol. 2003 Aug 1;66(3):459-69 15546153 - Am J Med Genet A. 2004 Dec 15;131(3):287-98 16051167 - Curr Biol. 2005 Jul 26;15(14):R563-74 12417261 - Biochem Pharmacol. 2002 Nov 15;64(10):1483-91 9141529 - J Clin Endocrinol Metab. 1997 May;82(5):1434-9 11178870 - Mol Cell Neurosci. 2001 Feb;17(2):329-41 10349836 - J Neurochem. 1999 Jun;72(6):2278-85 1333943 - Cytometry. 1992;13(8):795-808 1967820 - Nature. 1990 Feb 1;343(6257):425-30 8811180 - Annu Rev Biochem. 1996;65:241-69 15519853 - Trends Cell Biol. 2004 Nov;14(11):639-47 458444 - J Neurochem. 1979 Jul;33(1):107-15 12670506 - Biochem Biophys Res Commun. 2003 Apr 11;303(3):968-72 15153093 - Eur J Biochem. 2004 Jun;271(11):2050-5 12099998 - Clin Exp Pharmacol Physiol. 2002 Aug;29(8):673-8 6842086 - J Lipid Res. 1983 Mar;24(3):303-15 16111478 - J Neurochem. 2005 Sep;94(5):1277-87 10082972 - Biochim Biophys Acta. 1999 Mar 8;1449(2):137-49 7481820 - Science. 1995 Nov 24;270(5240):1326-31 6415164 - J Immunol. 1983 Nov;131(5):2362-7 15374955 - Cancer Res. 2004 Sep 15;64(18):6461-8 6903572 - J Clin Invest. 1980 Nov;66(5):1094-100 Blanco-Colio (2021112213350488700_B6) 2002; 161 Hetman (2021112213350488700_B26) 2004; 271 Rabelo (2021112213350488700_B43) 2003; 303 Brantley-Finley (2021112213350488700_B46) 2003; 66 Tanaka (2021112213350488700_B20) 2000; 20 Edison (2021112213350488700_B17) 2004; 350 Nakagawa (2021112213350488700_B35) 1998; 438 Blumenthal (2021112213350488700_B1) 2000; 139 Walton (2021112213350488700_B45) 2000; 23 Schulz (2021112213350488700_B21) 2004; 89 Goldstein (2021112213350488700_B4) 1990; 343 Cavender (2021112213350488700_B16) 1995; 269 Repasky (2021112213350488700_B24) 2004; 14 Jaster (2021112213350488700_B8) 2003; 65 Riccio (2021112213350488700_B42) 1999; 286 Villalonga (2021112213350488700_B31) 2002; 277 Nishida (2021112213350488700_B12) 2005; 269 Bonni (2021112213350488700_B28) 1999; 286 García-Román (2021112213350488700_B22) 2001; 17 Padayatty (2021112213350488700_B5) 1997; 82 Muñoz (2021112213350488700_B30) 1993; 121 Johnson (2021112213350488700_B38) 2002; 56 Edison (2021112213350488700_B18) 2004; 131 Hillyard (2021112213350488700_B7) 2002; 29 Skaletz-Rorowski (2021112213350488700_B40) 2001; 80 Koyuturk (2021112213350488700_B9) 2004; 370 Xia (2021112213350488700_B27) 1995; 270 Chong (2021112213350488700_B2) 2001; 111 Takata (2021112213350488700_B10) 2004; 13 Wu (2021112213350488700_B11) 2004; 64 Maltese (2021112213350488700_B14) 1979; 33 Negre-Aminou (2021112213350488700_B41) 2002; 64 Bassa (2021112213350488700_B36) 1999; 1449 Kita (2021112213350488700_B29) 1980; 66 Denhardt (2021112213350488700_B23) 1996; 318 Drysdale (2021112213350488700_B32) 1983; 131 Cerezo-Guisado (2021112213350488700_B34) 2005; 94 Graaf (2021112213350488700_B3) 2004; 30 Graham (2021112213350488700_B39) 1998; 161 Michikawa (2021112213350488700_B19) 1999; 72 Darzynkiewicz (2021112213350488700_B33) 1992; 13 Miura (2021112213350488700_B37) 2004; 175 Hansen (2021112213350488700_B44) 2004; 16 Spady (2021112213350488700_B15) 1983; 24 Zhang (2021112213350488700_B13) 1996; 65 Mitin (2021112213350488700_B25) 2005; 15 |
References_xml | – volume: 438 start-page: 289 year: 1998 ident: 2021112213350488700_B35 article-title: HMG-CoA reductase inhibitor-induced L6 myoblast cell death: involvement of the phosphatidylinositol 3-kinase pathway publication-title: FEBS Lett. doi: 10.1016/S0014-5793(98)01320-9 contributor: fullname: Nakagawa – volume: 286 start-page: 1358 year: 1999 ident: 2021112213350488700_B28 article-title: Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and independent mechanisms publication-title: Science doi: 10.1126/science.286.5443.1358 contributor: fullname: Bonni – volume: 33 start-page: 107 year: 1979 ident: 2021112213350488700_B14 article-title: Developmental changes in the distribution of 3-hydroxy-3-methylglutaryl coenzyme A reductase among subcellular fractions of rat brain publication-title: J. Neurochem. doi: 10.1111/j.1471-4159.1979.tb11712.x contributor: fullname: Maltese – volume: 318 start-page: 729 year: 1996 ident: 2021112213350488700_B23 article-title: Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell: the potential for multiplex signalling publication-title: Biochem. J. doi: 10.1042/bj3180729 contributor: fullname: Denhardt – volume: 23 start-page: 48 year: 2000 ident: 2021112213350488700_B45 article-title: Is CREB a key to neuronal survival? publication-title: Trends Neurosci. doi: 10.1016/S0166-2236(99)01500-3 contributor: fullname: Walton – volume: 175 start-page: 235 year: 2004 ident: 2021112213350488700_B37 article-title: Simvastatin suppresses coronary artery endotelial tube formation by disrupting Ras/Raf/ERK signaling publication-title: Atherosclerosis doi: 10.1016/j.atherosclerosis.2004.04.017 contributor: fullname: Miura – volume: 13 start-page: 41 year: 2004 ident: 2021112213350488700_B10 article-title: Cerivastatin-induced apoptosis of human aortic smooth muscle cells through partial inhibition of basal activation of extracellular signal-regulated kinases publication-title: Cardiovasc. Pathol. doi: 10.1016/S1054-8807(03)00104-2 contributor: fullname: Takata – volume: 66 start-page: 1094 year: 1980 ident: 2021112213350488700_B29 article-title: Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in livers of mice treated with mevilonin, a competitive inhibitor of the reductase publication-title: J. Clin. Invest. doi: 10.1172/JCI109938 contributor: fullname: Kita – volume: 56 start-page: 133 year: 2002 ident: 2021112213350488700_B38 article-title: Lovastatin is a potent inhibitor of meningioma cell proliferation: evidence for inhibition of a mitogen associated protein kinase publication-title: J. Neurooncol. doi: 10.1023/A:1014588214966 contributor: fullname: Johnson – volume: 350 start-page: 1579 year: 2004 ident: 2021112213350488700_B17 article-title: Central nervous system and limb anomalies in case reports of first-trimester statin exposure publication-title: N. Engl. J. Med. doi: 10.1056/NEJM200404083501524 contributor: fullname: Edison – volume: 17 start-page: 329 year: 2001 ident: 2021112213350488700_B22 article-title: Lovastatin induces apoptosis of spontaneously immortalized rat brain neuroblasts: involvement of nonsterol isoprenoid biosynthesis inhibition publication-title: Mol. Cell. Neurosci. doi: 10.1006/mcne.2000.0904 contributor: fullname: García-Román – volume: 13 start-page: 795 year: 1992 ident: 2021112213350488700_B33 article-title: Features of apoptotic cells measured by flow cytometry publication-title: Cytometry doi: 10.1002/cyto.990130802 contributor: fullname: Darzynkiewicz – volume: 16 start-page: 440 year: 2004 ident: 2021112213350488700_B44 article-title: Mechanisms leading to disseminated apoptosis following NMDA receptor blockade in the developing rat brain publication-title: Neurobiol. Dis. doi: 10.1016/j.nbd.2004.03.013 contributor: fullname: Hansen – volume: 82 start-page: 1434 year: 1997 ident: 2021112213350488700_B5 article-title: Lovastatin-induced apoptosis in prostate stromal cells publication-title: J. Clin. Endocr. Metab. doi: 10.1210/jcem.82.5.3960 contributor: fullname: Padayatty – volume: 271 start-page: 2050 year: 2004 ident: 2021112213350488700_B26 article-title: Role of extracellular signal regulated kinases 1 and 2 in neuronal survival publication-title: Eur. J. Biochem. doi: 10.1111/j.1432-1033.2004.04133.x contributor: fullname: Hetman – volume: 111 start-page: 390 year: 2001 ident: 2021112213350488700_B2 article-title: Clinically relevant differences between the statins: implications for therapeutic selection publication-title: Am. J. Med. doi: 10.1016/S0002-9343(01)00870-1 contributor: fullname: Chong – volume: 29 start-page: 673 year: 2002 ident: 2021112213350488700_B7 article-title: Inhibition of proliferation and signalling mechanisms in human lymphocytes by fluvastatin publication-title: Clin. Exp. Pharmacol. P. doi: 10.1046/j.1440-1681.2002.03711.x contributor: fullname: Hillyard – volume: 343 start-page: 425 year: 1990 ident: 2021112213350488700_B4 article-title: Regulation of the mevalonate pathway publication-title: Nature doi: 10.1038/343425a0 contributor: fullname: Goldstein – volume: 370 start-page: 212 year: 2004 ident: 2021112213350488700_B9 article-title: Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-Jun N-terminal kinase publication-title: Neurosci. Lett. doi: 10.1016/j.neulet.2004.08.020 contributor: fullname: Koyuturk – volume: 20 start-page: 2852 year: 2000 ident: 2021112213350488700_B20 article-title: Geranylgeranyl-pirophosphate, an isoprenoid of mevalonate cascade, is a critical compound for rat primary cultured cortical neurons to protect the cell death induced by 3-hydroxy-3-methylglutaryl-CoA reductase inhibition publication-title: J. Neurosci. doi: 10.1523/JNEUROSCI.20-08-02852.2000 contributor: fullname: Tanaka – volume: 270 start-page: 1326 year: 1995 ident: 2021112213350488700_B27 article-title: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis publication-title: Science doi: 10.1126/science.270.5240.1326 contributor: fullname: Xia – volume: 24 start-page: 303 year: 1983 ident: 2021112213350488700_B15 article-title: Sterol synthesis in vivo in 18 tissues of the squirrell monkey, guinea pig, rabbit, hamster and rat publication-title: J. Lipids Res. doi: 10.1016/S0022-2275(20)37999-2 contributor: fullname: Spady – volume: 269 start-page: E331 year: 1995 ident: 2021112213350488700_B16 article-title: Sterol metabolism in fetal, newborn and suckled lambs and their response to cholesterol after weaning publication-title: Am. J. Physiol. contributor: fullname: Cavender – volume: 139 start-page: 577 year: 2000 ident: 2021112213350488700_B1 article-title: Statins: effective antiatherosclerotic therapy publication-title: Am. Heart J. doi: 10.1016/S0002-8703(00)90033-4 contributor: fullname: Blumenthal – volume: 94 start-page: 1277 year: 2005 ident: 2021112213350488700_B34 article-title: Lovastatin inhibits the growth and survival pathway of phosphoinositide 3-kinase/protein kinase B in immortalized rat brain neuroblasts publication-title: J. Neurochem. doi: 10.1111/j.1471-4159.2005.03345.x contributor: fullname: Cerezo-Guisado – volume: 286 start-page: 2358 year: 1999 ident: 2021112213350488700_B42 article-title: Mediation by CREB family transcription factor of NGF-dependent survival of sympathetic neurons publication-title: Science doi: 10.1126/science.286.5448.2358 contributor: fullname: Riccio – volume: 72 start-page: 2278 year: 1999 ident: 2021112213350488700_B19 article-title: Inhibition of cholesterol production but not of nonsterol isoprenoid products induces neuronal cell death publication-title: J. Neurochem. doi: 10.1046/j.1471-4159.1999.0722278.x contributor: fullname: Michikawa – volume: 269 start-page: 109 year: 2005 ident: 2021112213350488700_B12 article-title: Mevastatin induces apoptosis in HL60 cells dependently on decrease in phosphorylated ERK publication-title: Mol. Cell. Biochem. doi: 10.1007/s11010-005-3086-0 contributor: fullname: Nishida – volume: 64 start-page: 1483 year: 2002 ident: 2021112213350488700_B41 article-title: Differential effect of simvastatin on activation of Rac(1) vs. activation of the heat shock protein 27-mediated pathway upon oxidative stress, in human smooth muscle cells publication-title: Biochem. Pharmacol. doi: 10.1016/S0006-2952(02)01388-6 contributor: fullname: Negre-Aminou – volume: 303 start-page: 968 year: 2003 ident: 2021112213350488700_B43 article-title: Inhibition of ERK1/2 and CREB phosphorylation by caspase-dependent mechanism enhances apoptosis in fibrosarcoma cell line treated with butyrate publication-title: Biochem. Bioph. Res. Commun. doi: 10.1016/S0006-291X(03)00454-6 contributor: fullname: Rabelo – volume: 64 start-page: 6461 year: 2004 ident: 2021112213350488700_B11 article-title: Blocking the Raf/MEK/ERK pathway sensitizes acute myelogenous leukaemia cells to lovastatin-induced apoptosis publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-04-0866 contributor: fullname: Wu – volume: 121 start-page: 423 year: 1993 ident: 2021112213350488700_B30 article-title: Thyroid hormone receptor/c-erbA: control of commitment and differentiation in the neuronal/chromaffin progenitor line PC12 publication-title: J. Cell Biol. doi: 10.1083/jcb.121.2.423 contributor: fullname: Muñoz – volume: 131 start-page: 287 year: 2004 ident: 2021112213350488700_B18 article-title: Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestational exposure to statins publication-title: Am. J. Med. Genet. doi: 10.1002/ajmg.a.30386 contributor: fullname: Edison – volume: 66 start-page: 459 year: 2003 ident: 2021112213350488700_B46 article-title: The JNK, ERK and p53 pathways play distinct roles in apoptosis mediated by the antitumor agents vinblastine, doxorubicin, and etoposide publication-title: Biochem. Pharmacol. doi: 10.1016/S0006-2952(03)00255-7 contributor: fullname: Brantley-Finley – volume: 89 start-page: 24 year: 2004 ident: 2021112213350488700_B21 article-title: HMG-CoA reductase inhibition causes neurite loss by interfering with geranylgeranylpyrophosphate synthesis publication-title: J. Neurochem. doi: 10.1046/j.1471-4159.2003.02305.x contributor: fullname: Schulz – volume: 15 start-page: R563 year: 2005 ident: 2021112213350488700_B25 article-title: Signaling interplay in ras superfamily function publication-title: Curr. Biol. doi: 10.1016/j.cub.2005.07.010 contributor: fullname: Mitin – volume: 14 start-page: 639 year: 2004 ident: 2021112213350488700_B24 article-title: Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis? publication-title: Trends Cell. Biol. doi: 10.1016/j.tcb.2004.09.014 contributor: fullname: Repasky – volume: 277 start-page: 37929 year: 2002 ident: 2021112213350488700_B31 article-title: Calmodulin prevents activation of Ras by PKC in 3T3 fibroblasts publication-title: J. Biol. Chem. doi: 10.1074/jbc.M202245200 contributor: fullname: Villalonga – volume: 131 start-page: 2362 year: 1983 ident: 2021112213350488700_B32 article-title: Mechanism of macrophage-mediated cytotoxicity: production of a soluble cytotoxic factor publication-title: J. Immunol. doi: 10.4049/jimmunol.131.5.2362 contributor: fullname: Drysdale – volume: 80 start-page: 207 year: 2001 ident: 2021112213350488700_B40 article-title: Lovastatin blocks basis fibroblast growth factor-induced mitogen-activated protein kinase signalling in coronary smooth muscle cells via phosphatase inhibition publication-title: Eur. J. Cell. Biol. doi: 10.1078/0171-9335-00155 contributor: fullname: Skaletz-Rorowski – volume: 30 start-page: 609 year: 2004 ident: 2021112213350488700_B3 article-title: Effect of statins and farnesyltransferase inhibitors on the development and progression of cancer publication-title: Cancer Treat. Rev. doi: 10.1016/j.ctrv.2004.06.010 contributor: fullname: Graaf – volume: 161 start-page: 6733 year: 1998 ident: 2021112213350488700_B39 article-title: MEK and ERK activation in Ras-disabled RBL-2H3 mast cells and novel roles for geranylgeranylated and farnesylated proteins in FcϵRI-mediated signaling publication-title: J. Immunol. doi: 10.4049/jimmunol.161.12.6733 contributor: fullname: Graham – volume: 1449 start-page: 137 year: 1999 ident: 2021112213350488700_B36 article-title: Effect of inhibition of cholesterol synthetic pathway on the activation of Ras and MAP kinase in mesangial cells publication-title: Biochim. Biophys. Acta doi: 10.1016/S0167-4889(99)00007-5 contributor: fullname: Bassa – volume: 65 start-page: 241 year: 1996 ident: 2021112213350488700_B13 article-title: Protein prenylation: molecular mechanisms and functional consequences publication-title: Annu. Rev. Biochem. doi: 10.1146/annurev.bi.65.070196.001325 contributor: fullname: Zhang – volume: 65 start-page: 1295 year: 2003 ident: 2021112213350488700_B8 article-title: Inhibition of pancreatic stellate cell activation by the hydroxymethylglutaryl coenzyme A reductase inhibitor lovastatin publication-title: Biochem. Pharmacol. doi: 10.1016/S0006-2952(03)00075-3 contributor: fullname: Jaster – volume: 161 start-page: 17 year: 2002 ident: 2021112213350488700_B6 article-title: 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, atorvastatin and simvastatin, induce apoptosis of vascular smooth muscle cells by downregulation of Bcl-2 expression and Rho A prenylation publication-title: Atherosclerosis doi: 10.1016/S0021-9150(01)00613-X contributor: fullname: Blanco-Colio |
SSID | ssj0014040 |
Score | 2.1086452 |
Snippet | We have shown previously that lovastatin, a 3-hydroxy-3-methyl- glutaryl coenzyme A reductase inhibitor, induces apoptosis in spontaneously immortalized rat... We have shown previously that lovastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, induces apoptosis in spontaneously immortalized rat... We have previously shown that lovastatin, an HMG-CoA reductase inhibitor, induces apoptosis in spontaneously immortalized rat brain neuroblasts. In the present... |
SourceID | pubmedcentral hal proquest crossref pubmed |
SourceType | Open Access Repository Aggregation Database Index Database |
StartPage | 175 |
SubjectTerms | Animals beta-Galactosidase - genetics beta-Galactosidase - metabolism Brain - enzymology Cells, Cultured Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors Fetus Genes, Reporter Lovastatin - pharmacology Luciferases - metabolism Neurons - cytology Neurons - drug effects Neurons - enzymology Rats |
Title | Lovastatin inhibits the extracellular-signal-regulated kinase pathway in immortalized rat brain neuroblasts |
URI | https://www.ncbi.nlm.nih.gov/pubmed/16952276 https://search.proquest.com/docview/19639061 https://search.proquest.com/docview/68362934 https://hal.science/hal-00478598 https://pubmed.ncbi.nlm.nih.gov/PMC1698684 |
Volume | 401 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT9wwELZYLu2laqGPpQ-sturNbB6OYx-3K9AKQdVDkbhFdmxrI1iDdkMr-us74ySFLeLSa2xHlmc088348wwhn8FJ2bxOHRPaccaFt0ynqmTK5UZIKaT3-Dj59JuYn_Hj8-J8ixTDW5hI2q9NcxAulwehWURu5fWyngw8scn301kqFPyFT0ZkVOb5EKL3Vwc84X1ihTMBHmyoScqzyddjDKBBqWN_GKEAe2CtkXsOabRAOuRDrPkvZfKeDzp6Tp714JFOu02-IFsu7JDdaYDAeXlLv9BI54x58h3yZDa0ctslFyfIOMVL90CbsGhM064pID8KlnmlMXePZFSGXA59yVZde3pn6UUTwMlR7Fr8S99SXA1qi3i9-Q3DoDzUYIsJGqtiGgDi7folOTs6_DGbs77LAqsBCrVMJXVW1Kq0qdF5AQ4f5FU4kXovsszJzLrEZYlPrVOZBtNovDfWK6cFGANTuvwV2Q5Xwb0hNLHeQ5gLQZmT3AF4lInhXha8znMLYh-TT8NRV9ddMY0qXoLzrLqTzZh8BCn8nYD1r-fTkwq_YW1LWSj5EybtD0Kq4DDxpHRwVzfrCk2KApTy-AzYuACUw8fkdSfUu830OjEm5Ya4NzazOQI6Goty9zq5998r35KnXd4Y0zvvyHa7unHvAfC05kNU8D-swQLA |
link.rule.ids | 230,315,733,786,790,891,27955,27956,53825,53827 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lc9MwEN7p41AuQFsoAUo1wHBT4oesWMeQaSeUpMOhZXrzWLY08aRRO4kD0_56dv2gTRkOcLVkjyx90n4rfdoF-IhGKg8z33CZGsGFtDlPfdXnyoRaxrGMraXLyZMzOboQp5fR5QZE7V2YSrSf6aLrruZdV0wrbeXNPOu1OrHet8nQlwq_InqbsI3zNYhaJ705PBCeaLZWBJdow9qopCLofT4lFxphXWWIkQrZB0UbeWCSNqckiPyTbT4WTT6wQifP4Hvb_lp8MuuuSt3N7h6FdvznH3wOTxteygZ18S5sGLcH-wOHPvn8ln1ilVK02oLfg51hmyVuH2ZjErPSeb5jhZsWuiiXDEklw0V_kdKxAOlcOclE0iu-qDPfm5zNCof2k1FC5J_pLaO3cUaQK1DcYTHikmnKXsGqgJsaOX65fAEXJ8fnwxFvEjjwDFlWyZWXBVGm-rmv0zBCLoFQiIz0rZVBYOIgN54JPOvnRgUprrraWp1bZVKJ64zum_AlbLlrZ14B83Jr0YNGf8_EwiAvjT0tbByJLAxzRFQHPrRjmNzUcTqS6nxdBMn9oHfgPQ7v7woUWns0GCf0jMJmxpGKf2Clo3b0E-xM6qnUmevVMqHVSiEB-nsNbLhEAiU6cFCj5b4xDdg60F_D0Vpj1ksQHVW87wYNr__7zSPYGZ1Pxsn4y9nXN_Ck3p6mXaS3sFUuVuYQeVWp31Wz6Bf9KyTA |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLbYkIAXLhuXcpsFiDc3N8eJH0uhKqOb9sCkiZcojm0adfWqNgVtv55zcmHtEC97je3IsT_7fMf-cg4hH8BI6agIDBO54YwLq1keyIRJEymRpiK1Fn9OPjoW41N-eBafbaT6qkX7hSr77nzed-W01lYu5oXX6cS8k6NhICS8hXsLbb0dchfWbJh0jnp7gcB93h6vcCbAjnWRSXnofTpENxqgXWeJERIYCEYc2TBLO1MURf7LOG8KJzcs0egR-dF9QyNAmfXXleoXVzfCO97qIx-Thy0_pYOmyhNyx7g9sj9w4JvPL-lHWitG66P4PXJ_2GWL2yezCYpa8V7f0dJNS1VWKwrkksLmv8zxegD1rgzlIvk5W5qfmDbMaDorHdhRiomRf-eXFFvDykCXoLyCYsAnVZjFgtaBNxVw_Wr1lJyOvnwfjlmbyIEVwLYqJv0ijAuZ6EDlUQycAiARGxFYK8LQpKE2vgl9G2gjwxx2X2Wt0laaXMB-oxITPSO77sKZF4T62lrwpMHvMyk3wE9TX3GbxryIIg3I6pH33TxmiyZeR1bfs_Mwu574HnkHU_y3AobYHg8mGT7D8JlpLNNfUOmgQ0AGg4kjlTtzsV5luGtJIEL_rwEdF0CkeI88bxBz3ZkWcD2SbGFpqzPbJYCQOu53i4iXt255QO6dfB5lk6_H316RB80pNR4mvSa71XJt3gC9qtTbeiH9AQsyJ0A |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Lovastatin+inhibits+the+extracellular-signal-regulated+kinase+pathway+in+immortalized+rat+brain+neuroblasts&rft.jtitle=Biochemical+journal&rft.au=Cerezo-Guisado%2C+Maria%C2%A0Isabel&rft.au=Garc%C3%ADA-Rom%C3%A1n%2C+Natalia&rft.au=Garc%C3%ADa-Mar%C3%ADN%2C+Luis%C2%A0Jes%C3%BAs&rft.au=%C3%81lvarez-Barrientos%2C+Alberto&rft.date=2007-01-01&rft.issn=0264-6021&rft.eissn=1470-8728&rft.volume=401&rft.issue=1&rft.spage=175&rft.epage=183&rft_id=info:doi/10.1042%2FBJ20060731&rft.externalDBID=n%2Fa&rft.externalDocID=10_1042_BJ20060731 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0264-6021&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0264-6021&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0264-6021&client=summon |