RGD Reference Report - Type 10 adenylyl cyclase mediates mitochondrial Bax translocation and apoptosis of adult rat cardiomyocytes under simulated ischaemia/reperfusion. - Rat Genome Database

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Type 10 adenylyl cyclase mediates mitochondrial Bax translocation and apoptosis of adult rat cardiomyocytes under simulated ischaemia/reperfusion.

Authors: Appukuttan, Avinash  Kasseckert, Sascha A  Micoogullari, Mustafa  Flacke, Jan-Paul  Kumar, Sanjeev  Woste, Alexandra  Abdallah, Yaser  Pott, Lutz  Reusch, H Peter  Ladilov, Yury 
Citation: Appukuttan A, etal., Cardiovasc Res. 2012 Feb 1;93(2):340-9. doi: 10.1093/cvr/cvr306. Epub 2011 Nov 21.
RGD ID: 329337361
Pubmed: PMID:22106416   (View Abstract at PubMed)
DOI: DOI:10.1093/cvr/cvr306   (Journal Full-text)


AIMS: Apoptosis of cardiomyocytes significantly contributes to the development of post-ischaemic 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 ischaemia/reperfusion are still poorly understood. Here we aimed to analyse the role of the soluble adenylyl cyclase (sAC).
METHODS AND RESULTS: Adult rat cardiomyocytes were subjected to simulated in vitro ischaemia (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 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, sAC knock-down mediated by an adenovirus coding 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 mitochondrial oxygen radical 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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mitochondrion  IDA 329337361MMO:0000679RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adcy10  (adenylate cyclase 10)


Additional Information