Differential regulation of cardiac heme oxygenase‐1 and vascular endothelial growth factor mRNA expressions by hemin, heavy metals, heat shock and anoxia

Abstract

Increasing attention has been paid to the effects of hypoxia, heavy metals and heat shocks on gene expression and to the similarities in their actions. This paper compares mRNA levels of two putative hypoxia, heavy metal and heat shock sensitive genes: heine oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) in myocyte-enriched cultures of neonatal rat heart cells. HO-1 mRNA expression is stimulated by hemin, Cd 2÷, Co 2+ and heat shocks but not by Ni 2+ or Mn 2+. It is stimulated by long (13 h) but not by short (4 h) periods of anoxia. Conversely, VEGF mRNA expression is stimulated by short as well as long periods of anoxia, by Cd 2+, Co 2+, Ni 2+ and Mn 2+ but not by hemin or heat shocks. The results suggest that heavy metals, anoxia and heat shocks exert their effects on VEGF and HO-1 mRNA expression through separate though potentially overlapping mechanisms. Increased expressions of HO-1 and VEGF may be both cardioprotective under hypoxic! ischemic conditions.

Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma

“…54,55 VEGF secretion is induced in cells under hypoxic conditions. 56,57 As PDT consumes oxygen, it may generate hypoxic conditions in vivo. Hypoxia-induced stabilization of HIF (hypoxia inducible factor)-1a, followed by its binding to the HRE (hypoxia responsive element) in the VEGF promoter, is a major regulator of VEGF gene expression.…”

Haem oxygenase augments porcine granulosa cell apoptosis in vitro

“…However, the proportion of apoptotic cells was not altered by treatment with haemin in weakly associated PGCs. Because haemin and ZnPP IX were used previously as, respectively, a haem oxygenase substrate and a haem oxygenase inhibitor, to investigate the effect of haem oxygenase on various phenomena in many organs (Eyssen-Hernandez et al 1996, Ye & Laychock 1998, Duckers et al 2001, Alexandreanu & Lawson 2003, we used both compounds in this study. Although high concentrations of ZnPP IX decrease both haem oxygenase and NOS activities, it had been reported previously that, in concentrations lower than 1 µM, it was able to inhibit haem oxygenase activity but did not affect NOS activity (Appleton et al 1999).…”

“…Haem oxygenases are induced by various factors . Several authors have shown that HO-1 was induced by heat shock, heavy metals, hypoxia and endotoxin (Eyssen-Hernandez et al 1996, Carraway et al 1998, Panchenko et al 2000, Stuhlmeier 2000. Furthermore, HO-1 was induced by TNF- (Terry et al 1998), which is known to stimulate granulosa cell apoptosis (Kaipai et al 1996).…”

“…Three distinct variants of haem oxygenases have been identified in humans. HO-1 is an inducible enzyme, the synthesis of which is elicited by numerous stimulants such as cytokines, heat shock, heavy metals, hypoxia, endotoxins and oxidants that induce inflammatory damage (Yoshida et al 1988, Eyssen-Hernandez et al 1996, Carraway et al 1998, Panchenko et al 2000, Stuhlmeier 2000. In contrast, HO-2 is constitutively expressed and is concentrated mostly in the brain and testes (McCoubrey et al 1992.…”

Expression of vascular endothelial growth factor-b in human astrocytoma

“…The culture medium was Dulbecco's MEM supplemented with 10% fetal bovine serum, 100 units/ml penicillin, and 100 µg/ml streptomycin. Hypoxic conditions were generated as previously described (Eyssen-Hernandez et al, 1996). Brie y, the cells were washed with serum-free medium, incubated in Dulbecco's MEM supplemented with 1% fetal bovine serum for 24 h in a humidi ed atmosphere containing 5% CO 2 , further incubated for 6 h in an airtight container (Institut Gustave Roussy, Villejuif, France), and continuously flushed with a mixture of gases containing 5% CO 2 and 95% N 2 .…”