Reactive oxygen species involved in prenylflavonoids, icariin and icaritin, initiating cardiac differentiation of mouse embryonic stem cells
The significant promoting effects of some prenylflavonoids on cardiac differentiation of mouse embryonic stem (ES) cells via reactive oxygen species (ROS) signaling pathway were investigated. The most effective differentiation was facilitated by icariin (ICA), followed by icaritin (ICT), while desme...
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Published in | Journal of cellular biochemistry Vol. 103; no. 5; pp. 1536 - 1550 |
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Abstract | The significant promoting effects of some prenylflavonoids on cardiac differentiation of mouse embryonic stem (ES) cells via reactive oxygen species (ROS) signaling pathway were investigated. The most effective differentiation was facilitated by icariin (ICA), followed by icaritin (ICT), while desmethylicaritin (DICT) displayed the weakest but still significant inducible effect. Contrarily, DICT demonstrated the strongest anti‐oxidative activity while ICA displayed only little in vitro, which was well matched with the hydroxyl (OH) numbers and the positions in the molecular structures. Therefore, ROS signaling cascades were assumed to be involved in prenylflavonoids induced cardiomyogenesis. Treatment with ICA, intracellular ROS in embryoid bodies was rapidly elevated, which was abolished by the NADPH‐oxidase inhibitor apocynin; elimination of intracellular ROS by vitamin E or pyrrolidine dithiocarbamate (PDTC) inhibited ICA induced cardiomyogenesis; ROS‐sensitive extracellular‐regulated kinase 1, 2 (ERK1, 2) and p38 activation were further observed, the cardiomyogenesis was significantly inhibited in the presence of ERK1, 2 or p38 inhibitor U0126 or SB203580, indicating the roles of NADPH‐ROS‐MAPKs signaling cascades in prenylflavonoids induced cardiac differentiation. There was no difference in Nox4 NADPH oxidase expression between ICA and ICT treatments, however, ROS concentration in EBs after ICT administration was lower than that after ICA treatment, followed by less activation of ERK1, 2, and p38. These results revealed that the significant promoting effects of prenylflavonoids on cardiac differentiation was at least partly via ROS signaling cascades, and the facilitating abilities preferentially based on the nature of prenylflavonoids themselves, but anti‐oxidative activity determined by the OH numbers and the positions in the structures do influence the cardiomyogenesis in vitro. J. Cell. Biochem. 103: 1536–1550, 2008. © 2007 Wiley‐Liss, Inc. |
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AbstractList | The significant promoting effects of some prenylflavonoids on cardiac differentiation of mouse embryonic stem (ES) cells via reactive oxygen species (ROS) signaling pathway were investigated. The most effective differentiation was facilitated by icariin (ICA), followed by icaritin (ICT), while desmethylicaritin (DICT) displayed the weakest but still significant inducible effect. Contrarily, DICT demonstrated the strongest anti‐oxidative activity while ICA displayed only little in vitro, which was well matched with the hydroxyl (OH) numbers and the positions in the molecular structures. Therefore, ROS signaling cascades were assumed to be involved in prenylflavonoids induced cardiomyogenesis. Treatment with ICA, intracellular ROS in embryoid bodies was rapidly elevated, which was abolished by the NADPH‐oxidase inhibitor apocynin; elimination of intracellular ROS by vitamin E or pyrrolidine dithiocarbamate (PDTC) inhibited ICA induced cardiomyogenesis; ROS‐sensitive extracellular‐regulated kinase 1, 2 (ERK1, 2) and p38 activation were further observed, the cardiomyogenesis was significantly inhibited in the presence of ERK1, 2 or p38 inhibitor U0126 or SB203580, indicating the roles of NADPH‐ROS‐MAPKs signaling cascades in prenylflavonoids induced cardiac differentiation. There was no difference in Nox4 NADPH oxidase expression between ICA and ICT treatments, however, ROS concentration in EBs after ICT administration was lower than that after ICA treatment, followed by less activation of ERK1, 2, and p38. These results revealed that the significant promoting effects of prenylflavonoids on cardiac differentiation was at least partly via ROS signaling cascades, and the facilitating abilities preferentially based on the nature of prenylflavonoids themselves, but anti‐oxidative activity determined by the OH numbers and the positions in the structures do influence the cardiomyogenesis in vitro. J. Cell. Biochem. 103: 1536–1550, 2008. © 2007 Wiley‐Liss, Inc. The significant promoting effects of some prenylflavonoids on cardiac differentiation of mouse embryonic stem (ES) cells via reactive oxygen species (ROS) signaling pathway were investigated. The most effective differentiation was facilitated by icariin (ICA), followed by icaritin (ICT), while desmethylicaritin (DICT) displayed the weakest but still significant inducible effect. Contrarily, DICT demonstrated the strongest anti-oxidative activity while ICA displayed only little in vitro, which was well matched with the hydroxyl (OH) numbers and the positions in the molecular structures. Therefore, ROS signaling cascades were assumed to be involved in prenylflavonoids induced cardiomyogenesis. Treatment with ICA, intracellular ROS in embryoid bodies was rapidly elevated, which was abolished by the NADPH-oxidase inhibitor apocynin; elimination of intracellular ROS by vitamin E or pyrrolidine dithiocarbamate (PDTC) inhibited ICA induced cardiomyogenesis; ROS-sensitive extracellular-regulated kinase 1, 2 (ERK1, 2) and p38 activation were further observed, the cardiomyogenesis was significantly inhibited in the presence of ERK1, 2 or p38 inhibitor U0126 or SB203580, indicating the roles of NADPH-ROS-MAPKs signaling cascades in prenylflavonoids induced cardiac differentiation. There was no difference in Nox4 NADPH oxidase expression between ICA and ICT treatments, however, ROS concentration in EBs after ICT administration was lower than that after ICA treatment, followed by less activation of ERK1, 2, and p38. These results revealed that the significant promoting effects of prenylflavonoids on cardiac differentiation was at least partly via ROS signaling cascades, and the facilitating abilities preferentially based on the nature of prenylflavonoids themselves, but anti-oxidative activity determined by the OH numbers and the positions in the structures do influence the cardiomyogenesis in vitro. |
Author | Lou, Yi-Jia Liu, Jian Wang, Zhi-Qiang Wo, Yan-bo Hu, Ying Zhu, Dan-yan |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17985362$$D View this record in MEDLINE/PubMed |
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Notes | ArticleID:JCB21541 ark:/67375/WNG-G7QLX047-6 Yan-bo Wo and Dan-yan Zhu contributed equally to this work. istex:51CA3C698F4843B094A4318AA176905F83C8A073 National Natural Sciences Foundation of China - No. 30672564; No. 30600762; No. 30472112; No. 30171121 Key Grant of the Chinese Ministry of Education - No. 03088 International Joint Key Grant of Zhejiang Province - No. 2003C24005 Yan‐bo Wo and Dan‐yan Zhu contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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SubjectTerms | Animals cardiac differentiation Cell Differentiation - drug effects Cell Line embryonic stem cell Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Enzyme Inhibitors - pharmacology Flavonoids - pharmacology icariin icaritin MAP Kinase Signaling System - drug effects Mice Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors Mitogen-Activated Protein Kinase 3 - metabolism Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism NADPH Oxidase 4 NADPH Oxidases - antagonists & inhibitors NADPH Oxidases - metabolism p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors p38 Mitogen-Activated Protein Kinases - metabolism prenylflavonoid Reactive Oxygen Species |
Title | Reactive oxygen species involved in prenylflavonoids, icariin and icaritin, initiating cardiac differentiation of mouse embryonic stem cells |
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