Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes.

Abstract

We examined whether apoptosis occurs in cardiomyocytes by hypoxia in vitro. Neonatal rat cardiomyocytes and nonmyocytes were cultured in 95% N2-5% CO2 atmosphere to produce hypoxic conditions. DNA fragmentation into ultraviolet exposure,2,6 anticancer drugs,8-10 viral infection, 11-3 and hyperthermia,14 in a variety of tissues. Ischemia of the heart, which is usually caused by reduction of coronary flow, induces the death of cardiomyocytes and replacement by fibrosis. Although this cardiomyocyte death is classically believed to be induced via necrosis, which is the mechanism of accidental cell death, its precise mechanism remains unclear. It has been recently reported that ischemia induces apoptotic death in the liver15 and in the brain16 in vivo. Thus, in addition to necrotic death, the mechanism of cardiomyocyte death may be involved in the apoptotic process. © 1994 American Heart Association, Inc.myocytes and nonmyocytes as revealed by Northern blotting and in situ hybridization. In hypoxic conditions, Fas messenger RNA levels in cardiomyocytes were upregulated by twofold over controls, whereas those of nonmyocytes were downregulated. These results indicate that cardiomyocyte death by hypoxia can occur via apoptosis and that Fas antigen may be associated with the mechanism of this apoptotic process. (Circ Res. 1994;75:426-433.)

Upregulation of BNIP3 and translocation to mitochondria mediates cyanide-induced apoptosis in cortical cells

“…The mode of cortical cell death observed with cyanide is similar to that produced by hypoxia, however the initiation signal may be different (Tanaka et al, 1994;Halterman and Federoff, 1999). Cell hypoxia increases BNIP3 expression by activating hypoxia inducible factor 1 alpha (HIF-1α), thus stimulating BNIP3 gene transcription by binding to the hypoxia-response element (HRE) present in the BNIP3 promoter.…”

Hypoxia induces the expression of the pro-apoptotic gene BNIP3

“…44,45 However, the molecular mechanism through which hypoxia induces apoptosis is far from clear. Through microarray analysis of a neonatal rat cardiomyocyte subtracted cDNA library, we demonstrated that expression of the pro-apoptotic gene BNIP3 is dramatically upregulated during hypoxia.…”

Fas Expression and Apoptosis Correlate With Cardiac Dysfunction in Patients With Dilated Cardiomyopathy

“…The contribution of apoptosis to cell death of myocytes in cardiovascular disorders such as hypertension, 17 heart failure 18 and myocytic hypoxia, 6 has recently been investigated in animal models. In a study in rats, Cheng et al showed that overstretching of a single myocyte might be related to the expression of Fas and to programmed cell death, suggesting that apoptosis may cause dilatation of the chamber.…”