シクロフィリンDと脳保護

虚血性脳障害の誘因となる機構の中でもミトコンドリア機能不全は神経障害において近年注目されている病態である。ミトコンドリア機能不全は,殊にミトコンドリア透過性亢進(Mitochondrial Permeability Transition:MPT)と呼ばれる現象が重要で,ミトコンドリアを介した細胞死における初期の重要な現象でミトコンドリアマトリックスに存在するCypD(シクロフィリンD)蛋白の活性化やF1F0ATPsynthaseの関与によるMPTが注目されている。本稿では多機能を有するシクロフィリンDおよびMPTの役割について再考してみたい。...

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Published in蘇生 Vol. 43; no. 2; pp. 52 - 59
Main Authors 松本, りか, 関根, 秀介, 山田, 利香子, 小野, 亜矢, 内野, 博之, 小林, 賢礼
Format Journal Article
LanguageJapanese
Published 日本蘇生学会 26.09.2024
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Online AccessGet full text
ISSN0288-4348
1884-748X
DOI10.11414/jjreanimatology.43.2_52

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Abstract 虚血性脳障害の誘因となる機構の中でもミトコンドリア機能不全は神経障害において近年注目されている病態である。ミトコンドリア機能不全は,殊にミトコンドリア透過性亢進(Mitochondrial Permeability Transition:MPT)と呼ばれる現象が重要で,ミトコンドリアを介した細胞死における初期の重要な現象でミトコンドリアマトリックスに存在するCypD(シクロフィリンD)蛋白の活性化やF1F0ATPsynthaseの関与によるMPTが注目されている。本稿では多機能を有するシクロフィリンDおよびMPTの役割について再考してみたい。
AbstractList 虚血性脳障害の誘因となる機構の中でもミトコンドリア機能不全は神経障害において近年注目されている病態である。ミトコンドリア機能不全は,殊にミトコンドリア透過性亢進(Mitochondrial Permeability Transition:MPT)と呼ばれる現象が重要で,ミトコンドリアを介した細胞死における初期の重要な現象でミトコンドリアマトリックスに存在するCypD(シクロフィリンD)蛋白の活性化やF1F0ATPsynthaseの関与によるMPTが注目されている。本稿では多機能を有するシクロフィリンDおよびMPTの役割について再考してみたい。
「要旨」虚血性脳障害の誘因となる機構の中でもミトコンドリア機能不全は神経障害において近年注目されている病態である. ミトコンドリア機能不全は, 殊にミトコンドリア透過性亢進(Mitochondrial Permeability Transition: MPT)と呼ばれる現象が重要で, ミトコンドリアを介した細胞死における初期の重要な現象でミトコンドリアマトリックスに存在するCypD(シクロフィリンD)蛋白の活性化やF1F0ATPsynthaseの関与によるMPTが注目されている. 本稿では多機能を有するシクロフィリンDおよびMPTの役割について再考してみたい.
Author 内野, 博之
小林, 賢礼
山田, 利香子
松本, りか
小野, 亜矢
関根, 秀介
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References 8) Hansen K. G., Herrmann J. M.:Transport of Proteins into Mitochondria. Protein J 38:330-342, 2019
31) Gautier C. A., Giaime E., Caballero E., ほか:Regulation of mitochondrial permeability transition pore by PINK1. Mol Neurodegener 7:22, 2012
16) Kim J. S., Wang J. H., Lemasters J. J.:Mitochondrial permeability transition in rat hepatocytes after anoxia/reoxygenation:role of Ca2+-dependent mitochondrial formation of reactive oxygen species. Am J Physiol Gastrointest Liver Physiol 302:G723-731, 2012
34) Demuro A., Parker I., Stutzmann G. E.:Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem 285:12463-12468, 2010
39) Zheng Y., Shi Y., Tian C., ほか:Essential role of the voltage-dependent anion channel (VDAC) in mitochondrial permeability transition pore opening and cytochrome c release induced by arsenic trioxide. Oncogene 23:1239-1247, 2004
3) 内野博之:脳障害の機序とミトコンドリア機能不全について シクロフィリンDを標的とした神経保護.蘇生 39:113, 2020
20) Price E. R., Zydowsky L. D., Jin M. J., ほか:Human cyclophilin B:a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence. Proc Natl Acad Sci U S A 88:1903-1907, 1991
5) Crompton M., Virji S., Ward J. M.:Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore. Eur J Biochem 258:729-735, 1998
19) Yang H., Chen J., Yang J., ほか:Cyclophilin A is upregulated in small cell lung cancer and activates ERK1/2 signal. Biochem Biophys Res Commun 361:763-767, 2007
27) Nakagawa T., Shimizu S., Watanabe T., ほか:Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434:652-658, 2005
15) Colgan J., Asmal M., Yu B., ほか:Cyclophilin A-deficient mice are resistant to immunosuppression by cyclosporine. J Immunol 174:6030-6038, 2005
40) Baines C. P., Kaiser R. A., Sheiko T., ほか:Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9:550-555, 2007
9) Baines C. P., Kaiser R. A., Purcell N. H., ほか:Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658-662, 2005
30) Du H., Guo L., Fang F., ほか:Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 14:1097-1105, 2008
41) Beutner G., Alanzalon R. E., Porter G. A., Jr.:Cyclophilin D regulates the dynamic assembly of mitochondrial ATP synthase into synthasomes. Sci Rep 7:14488, 2017
23) Elrod J. W., Molkentin J. D.:Physiologic functions of cyclophilin D and the mitochondrial permeability transition pore. Circ J 77:1111-1122, 2013
28) Martin L. J., Semenkow S., Hanaford A., ほか:Mitochondrial permeability transition pore regulates Parkinson's disease development in mutant alpha-synuclein transgenic mice. Neurobiol Aging 35:1132-1152, 2014
18) Satoh K., Nigro P., Matoba T., ほか:Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms. Nat Med 15:649-656, 2009
35) Hansson Petersen C. A., Alikhani N., Behbahani H., ほか:The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 105:13145-13150, 2008
22) Waldmeier P. C., Zimmermann K., Qian T., ほか:Cyclophilin D as a drug target. Curr Med Chem 10:1485-1506, 2003
38) Singh P., Suman S., Chandna S., ほか:Possible role of amyloid-beta, adenine nucleotide translocase and cyclophilin-D interaction in mitochondrial dysfunction of Alzheimer's disease. Bioinformation 3:440-445, 2009
21) Price E. R., Jin M., Lim D., ほか:Cyclophilin B trafficking through the secretory pathway is altered by binding of cyclosporin A. Proc Natl Acad Sci U S A 91:3931-3935, 1994
1) Moreira P. I., Custodio J. B., Oliveira C. R., ほか:Brain   mitochondrial injury induced by oxidative stress-related events is prevented by tamoxifen. Neuropharmacology 48:435-447, 2005
12) Handschumacher R. E., Harding M. W., Rice J., ほか:Cyclophilin:a specific cytosolic binding protein for cyclosporin A. Science 226:544-547, 1984
11) Wang Ping, Heitman Joseph:The cyclophilins. Genome Biology 6:226, 2005
13) )Fischer G., Wittmann-Liebold B., Lang K., ほか:Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature 337:476-478, 1989
32) Haass C., Selkoe D. J.:Soluble protein oligomers in neurodegeneration:lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101-112, 2007
24) Rasola A., Bernardi P.:Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis. Cell Calcium 50:222-233, 2011
7) Giacomello M., Pyakurel A., Glytsou C., ほか:The cell   biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol 21:204-224, 2020
25) Linkermann A., Green D. R.:Necroptosis. N Engl J Med 370:455-465, 2014
37) Beck S. J., Guo L., Phensy A., ほか:Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer's disease. Nat Commun 7:11483, 2016
10) Giorgio Valentina, Von Stockum Sophia, Antoniel Manuela, ほか:Dimers of mitochondrial ATP synthase form the permeability transition pore. Proceedings of the National Academy of Sciences 110:5887-5892, 2013
14) Anderson S. K., Gallinger S., Roder J., ほか:A cyclophilin-related protein involved in the function of natural killer cells. Proc Natl Acad Sci U S A 90:542-546, 1993
6) Crompton M.:The mitochondrial permeability transition pore and its role in cell death. Biochem J 341 (Pt 2):233-249, 1999
29) Crofts A. R., Chappell J. B.:Calcium Ion Accumulation and Volume Changes of Isolated Liver Mitochondria. Reversal of Calcium Ion-Induced Swelling. Biochem J 95:387-392, 1965
2) 内野博之,福井秀公,宮下亮一,ほか:虚血性脳障害のメカニズム.蘇生 32:94-105, 2013
42) Bonora Massimo, Giorgi Carlotta, Pinton Paolo:Molecular mechanisms and consequences of mitochondrial permeability transition. Nature Reviews Molecular Cell Biology 23:266-285, 2022
33) Rao V. K., Carlson E. A., Yan S. S.:Mitochondrial permeability transition pore is a potential drug target for neurodegeneration. Biochim Biophys Acta 1842:1267-1272, 2014
36) Elkamhawy A., Lee J., Park B. G., ほか:Novel quinazoline-urea analogues as modulators for Abeta-induced mitochondrial dysfunction:design, synthesis, and molecular docking study. Eur J Med Chem 84:466-475, 2014
4) 内野博之,原 直美,石田裕介,ほか:脳救急医学と脊髄・新生児脳障害 虚血性脳障害とミトコンドリア機能不全.脳循環代謝 26:155-161, 2015
26) Linkermann Andreas, Bräsen Jan Hinrich, Darding Maurice, ほか:Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proceedings of the National Academy of Sciences 110:12024-12029, 2013
17) Arora K., Gwinn W. M., Bower M. A., ほか:Extracellular cyclophilins contribute to the regulation of inflammatory responses. J Immunol 175:517-522, 2005
References_xml – reference: 2) 内野博之,福井秀公,宮下亮一,ほか:虚血性脳障害のメカニズム.蘇生 32:94-105, 2013
– reference: 11) Wang Ping, Heitman Joseph:The cyclophilins. Genome Biology 6:226, 2005
– reference: 28) Martin L. J., Semenkow S., Hanaford A., ほか:Mitochondrial permeability transition pore regulates Parkinson's disease development in mutant alpha-synuclein transgenic mice. Neurobiol Aging 35:1132-1152, 2014
– reference: 27) Nakagawa T., Shimizu S., Watanabe T., ほか:Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434:652-658, 2005
– reference: 15) Colgan J., Asmal M., Yu B., ほか:Cyclophilin A-deficient mice are resistant to immunosuppression by cyclosporine. J Immunol 174:6030-6038, 2005
– reference: 14) Anderson S. K., Gallinger S., Roder J., ほか:A cyclophilin-related protein involved in the function of natural killer cells. Proc Natl Acad Sci U S A 90:542-546, 1993
– reference: 37) Beck S. J., Guo L., Phensy A., ほか:Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer's disease. Nat Commun 7:11483, 2016
– reference: 4) 内野博之,原 直美,石田裕介,ほか:脳救急医学と脊髄・新生児脳障害 虚血性脳障害とミトコンドリア機能不全.脳循環代謝 26:155-161, 2015
– reference: 32) Haass C., Selkoe D. J.:Soluble protein oligomers in neurodegeneration:lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101-112, 2007
– reference: 22) Waldmeier P. C., Zimmermann K., Qian T., ほか:Cyclophilin D as a drug target. Curr Med Chem 10:1485-1506, 2003
– reference: 17) Arora K., Gwinn W. M., Bower M. A., ほか:Extracellular cyclophilins contribute to the regulation of inflammatory responses. J Immunol 175:517-522, 2005
– reference: 6) Crompton M.:The mitochondrial permeability transition pore and its role in cell death. Biochem J 341 (Pt 2):233-249, 1999
– reference: 12) Handschumacher R. E., Harding M. W., Rice J., ほか:Cyclophilin:a specific cytosolic binding protein for cyclosporin A. Science 226:544-547, 1984
– reference: 16) Kim J. S., Wang J. H., Lemasters J. J.:Mitochondrial permeability transition in rat hepatocytes after anoxia/reoxygenation:role of Ca2+-dependent mitochondrial formation of reactive oxygen species. Am J Physiol Gastrointest Liver Physiol 302:G723-731, 2012
– reference: 13) )Fischer G., Wittmann-Liebold B., Lang K., ほか:Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature 337:476-478, 1989
– reference: 9) Baines C. P., Kaiser R. A., Purcell N. H., ほか:Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658-662, 2005
– reference: 10) Giorgio Valentina, Von Stockum Sophia, Antoniel Manuela, ほか:Dimers of mitochondrial ATP synthase form the permeability transition pore. Proceedings of the National Academy of Sciences 110:5887-5892, 2013
– reference: 25) Linkermann A., Green D. R.:Necroptosis. N Engl J Med 370:455-465, 2014
– reference: 38) Singh P., Suman S., Chandna S., ほか:Possible role of amyloid-beta, adenine nucleotide translocase and cyclophilin-D interaction in mitochondrial dysfunction of Alzheimer's disease. Bioinformation 3:440-445, 2009
– reference: 35) Hansson Petersen C. A., Alikhani N., Behbahani H., ほか:The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 105:13145-13150, 2008
– reference: 5) Crompton M., Virji S., Ward J. M.:Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore. Eur J Biochem 258:729-735, 1998
– reference: 8) Hansen K. G., Herrmann J. M.:Transport of Proteins into Mitochondria. Protein J 38:330-342, 2019
– reference: 19) Yang H., Chen J., Yang J., ほか:Cyclophilin A is upregulated in small cell lung cancer and activates ERK1/2 signal. Biochem Biophys Res Commun 361:763-767, 2007
– reference: 30) Du H., Guo L., Fang F., ほか:Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 14:1097-1105, 2008
– reference: 21) Price E. R., Jin M., Lim D., ほか:Cyclophilin B trafficking through the secretory pathway is altered by binding of cyclosporin A. Proc Natl Acad Sci U S A 91:3931-3935, 1994
– reference: 23) Elrod J. W., Molkentin J. D.:Physiologic functions of cyclophilin D and the mitochondrial permeability transition pore. Circ J 77:1111-1122, 2013
– reference: 42) Bonora Massimo, Giorgi Carlotta, Pinton Paolo:Molecular mechanisms and consequences of mitochondrial permeability transition. Nature Reviews Molecular Cell Biology 23:266-285, 2022
– reference: 20) Price E. R., Zydowsky L. D., Jin M. J., ほか:Human cyclophilin B:a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence. Proc Natl Acad Sci U S A 88:1903-1907, 1991
– reference: 36) Elkamhawy A., Lee J., Park B. G., ほか:Novel quinazoline-urea analogues as modulators for Abeta-induced mitochondrial dysfunction:design, synthesis, and molecular docking study. Eur J Med Chem 84:466-475, 2014
– reference: 40) Baines C. P., Kaiser R. A., Sheiko T., ほか:Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9:550-555, 2007
– reference: 1) Moreira P. I., Custodio J. B., Oliveira C. R., ほか:Brain   mitochondrial injury induced by oxidative stress-related events is prevented by tamoxifen. Neuropharmacology 48:435-447, 2005
– reference: 29) Crofts A. R., Chappell J. B.:Calcium Ion Accumulation and Volume Changes of Isolated Liver Mitochondria. Reversal of Calcium Ion-Induced Swelling. Biochem J 95:387-392, 1965
– reference: 24) Rasola A., Bernardi P.:Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis. Cell Calcium 50:222-233, 2011
– reference: 33) Rao V. K., Carlson E. A., Yan S. S.:Mitochondrial permeability transition pore is a potential drug target for neurodegeneration. Biochim Biophys Acta 1842:1267-1272, 2014
– reference: 3) 内野博之:脳障害の機序とミトコンドリア機能不全について シクロフィリンDを標的とした神経保護.蘇生 39:113, 2020
– reference: 26) Linkermann Andreas, Bräsen Jan Hinrich, Darding Maurice, ほか:Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proceedings of the National Academy of Sciences 110:12024-12029, 2013
– reference: 31) Gautier C. A., Giaime E., Caballero E., ほか:Regulation of mitochondrial permeability transition pore by PINK1. Mol Neurodegener 7:22, 2012
– reference: 39) Zheng Y., Shi Y., Tian C., ほか:Essential role of the voltage-dependent anion channel (VDAC) in mitochondrial permeability transition pore opening and cytochrome c release induced by arsenic trioxide. Oncogene 23:1239-1247, 2004
– reference: 18) Satoh K., Nigro P., Matoba T., ほか:Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms. Nat Med 15:649-656, 2009
– reference: 34) Demuro A., Parker I., Stutzmann G. E.:Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem 285:12463-12468, 2010
– reference: 7) Giacomello M., Pyakurel A., Glytsou C., ほか:The cell   biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol 21:204-224, 2020
– reference: 41) Beutner G., Alanzalon R. E., Porter G. A., Jr.:Cyclophilin D regulates the dynamic assembly of mitochondrial ATP synthase into synthasomes. Sci Rep 7:14488, 2017
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Snippet 虚血性脳障害の誘因となる機構の中でもミトコンドリア機能不全は神経障害において近年注目されている病態である。ミトコンドリア機能不全は,殊にミトコンドリア透過性亢進(Mitochondrial Permeability...
「要旨」虚血性脳障害の誘因となる機構の中でもミトコンドリア機能不全は神経障害において近年注目されている病態である. ミトコンドリア機能不全は, 殊にミトコンドリア透過性亢進(Mitochondrial Permeability Transition: MPT)と呼ばれる現象が重要で,...
SourceID medicalonline
jstage
SourceType Publisher
StartPage 52
SubjectTerms FoF1ATPsynthase
シクロフィリンD
シンタゾーム
ミトコンドリア機能不全
ミトコンドリア透過性亢進
Title シクロフィリンDと脳保護
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ispartofPNX 蘇生, 2024/09/26, Vol.43(2), pp.52-59
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