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

摘要: Aims Apoptosis of cardiomyocytes significantly contributes to the development post-ischaemic cardiomyopathy. Although mitochondria have been suggested play a crucial role in this process, precise mechanisms controlling mitochondria-dependent apoptosis under ischaemia/reperfusion are still poorly understood. Here we aimed analyse soluble adenylyl cyclase (sAC). Methods and results Adult rat were subjected simulated vitro ischaemia (SI) consisting glucose-free anoxia at pH 6.4. was detected by DNA laddering, chromatin condensation, caspases cleavage. SI led translocation sAC mitochondrial depolarization followed cytochrome c release, caspase-9/-3 cleavage during reperfusion (SR). Pharmacological inhibition SI, but not SR, reduced SI/SR-induced injury apoptosis. Similarly, knock-down mediated an adenovirus coding for shRNA targeting prevented activation pathway Analysis link between revealed protein kinase A-dependent Bax phosphorylation Thr(167) its which subsequently caused oxygen radical formation release caspase-9 SR. Conclusion These suggest key SI-induced adult cardiomyocytes.