Relationship between hypoxia-induced apoptosis and caspases-3 activation, intracellular calcium overload in cardiomyocytes.
- Author:
Zhou ZHOU
1
;
Xiao-hua WANG
;
Guang-xu ZHU
;
Zheng-ping YU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; Calcium; metabolism; Caspase 3; metabolism; Cell Hypoxia; Cytochromes c; metabolism; Cytosol; metabolism; Male; Mitochondria; metabolism; Myocytes, Cardiac; cytology; metabolism; Rats; Rats, Wistar
- From: Chinese Journal of Applied Physiology 2005;21(1):10-14
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo explore the effects of hypoxia on Caspases activation in cardiomyocyte and role of intracellular calcium in this event in cardiomyocytes.
METHODSAfter hypoxia 0 min, 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, apoptotic cell percentage was determined with Hoechst 33342 straining. Expressions of Caspases-3 mRNA and release of mitochondrial cytochrome c in primary culture of cardiomyocytes were determined by using RT-PCR and Western blotting respectively.
RESULTSElevation of Cyt c in cytosol was in accordance with the decline in mitochondrial Cyt c content. Significant increase in Cyt c in cytosol appeared at 12 h post hypoxia and peaked at 24 h while Cyt c in mitochondria could not be detected at 24 h post hypoxia. Hypoxia up-regulated Caspases-3 mRNA expressions beginning at 3 h post hypoxia. Intracellular calcium overload occurred earlier than release of mitochondrial Cyt c and the activation of Caspase-3 during the hypoxic insult. Inhibition of Caspase-3 activation and pretreatment with calcium chelator BAPTA/AM offered a marked protective effect on hypoxia induced cardiomyocyte apoptosis.
CONCLUSIONHypoxia can induce mitochondrion-dependent Caspase-3 activation in cardiomyocytes and therefore leads to cell apoptosis. Increase of intracellular Ca2+ plays an important role in the activation of Caspase-3 and the induction of apoptosis in cardiomyocytes.