| Type 10 adenylyl cyclase mediates mitochondrial Bax translocation and apoptosis of adult rat cardiomyocyte under simulated ischemia/ reperfusion. | |
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MedLine Citation:
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PMID: 22106416 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims Apoptosis of cardiomyocytes significantly contributes to the development of post-ischemic cardiomyopathy. Although mitochondria have been suggested to play a crucial role in this process, the precise mechanisms controlling the mitochondria-dependent apoptosis in cardiomyocytes under ischemia/reperfusion are still poorly understood. Here we aimed to analyse the role of the soluble adenylyl cylclase (sAC).Methods and Results Adult rat cardiomyocytes were subjected to simulated in vitro ischemia (SI) consisting of glucose-free anoxia at pH 6.4. Apoptosis was detected by DNA-laddering, chromatin condensation and caspases cleavage. SI led to the translocation of sAC to the mitochondria and mitochondrial depolarization followed by a cytochrome c release, caspase-9 /-3 cleavage and apoptosis during simulated reperfusion (SR). Pharmacological inhibition of sAC during SI, but not during SR, significantly reduced the SI/SR-induced mitochondrial injury and apoptosis. Similarly, a sAC knock-down mediated by an adenovirus encoding for shRNA targeting sAC prevented the activation of the mitochondrial pathway of apoptosis. Analysis of the link between sAC and apoptosis revealed a sAC and protein kinase A dependent Bax phosphorylation at Thr(167) and its translocation to mitochondria during SI, which subsequently caused a mitochondrial oxygen radicals formation followed by cytochrome c release and caspase-9 cleavage during SR.Conclusion These results suggest a key role of sAC in SI-induced mitochondrial Bax translocation and activation of the mitochondrial pathway of apoptosis in adult cardiomyocytes. |
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Authors:
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Avinash Appukuttan; Sascha Andreas Kasseckert; Mustafa Micoogullari; Jan-Paul Flacke; Sanjeev Kumar; Alexandra Woste; Yaser Abdallah; Lutz Pott; H Peter Reusch; Yury Ladilov |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-21 |
Journal Detail:
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Title: Cardiovascular research Volume: - ISSN: 1755-3245 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Clinical Pharmacology, Ruhr-University Bochum, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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