Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

Abstract

Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury. Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion. Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins, Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion, enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group. Ischemia/ reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion, expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.

Protein Kinase Cδ Activation Induces Apoptosis in Response to Cardiac Ischemia and Reperfusion Damage

“…5B). Therefore, our findings support previous data suggesting that ischemia and reperfusion induces myocardial cell apoptosis (31,50,51) that is mediated by PKC␦ translocation to the mitochondria and the activation of the apoptotic effectors involving cytochrome c release, caspase 3 activation, PARP cleavage, and DNA fragmentation. …”

Changes in proHB-EGF expression after functional activation of the immune system cells

“…In addition, it was found that prolonged intermittent hypoxic exposure induces myocardial tolerance against H/R injury in association with an elevation of Bcl-2 protein level through NF-kB activation. This possibility is supported by recent studies that indicated that Bcl-2 overexpression limits apoptosis in I/R injury of heart and liver [28]. It is known that the relationship between p53 and ROS is multifactorial [11,13,18].…”

“…Fluorescence, arbitrary units Bcl-2 and Bcl-xl result in marked disruption of mitochondrial membranes and subsequent cytochrome c release and procaspase-3 activation [28]. In our study, short-term H/R resulted in a remarkable rise in ROS formation as well as in the induction of p53 protein content that was associated with a decrease in Bcl-2 protein level in mitochondria (Fig.…”

“…Although the fact of apoptosis induction during hypoxia was confirmed in several independent studies [19,28], the exact mechanisms of this effect remain unknown. It was reported that the Hif-1 gene overexpression might play a trigger role in this pro- Bcl-2 → β-actin → cess because Hif-1α can bind to the p53 and promote p53-dependent apoptosis [29].…”

The Hypoxic Transcriptome of the Retina: Identification of Factors with Potential Neuroprotective Activity

“…Similarly, hypoxic pretreatment can also protect other tissues like heart or brain against various toxic insults (Gidday et al 1994;Emerson et al 1999;Cai et al 2003;Dong et al 2003) suggesting that hypoxic preconditioning might induce a general protective response. Such a response might involve hypoxia-inducible-factor 1a which is stabilized in the retina after hypoxic exposure (Grimm et al 2002).…”