Hypoxia-induced Haem Oxygenase-1 gene expression in neonatal rat cardiac myocytes.

Abstract

BACKGROUND:

Haem oxygenase (HO-1), a heat shock or stress protein, is a rate-limiting enzyme in the conversion of pro-oxidant haem to biliverdin and carbon monoxide (CO). The products of haem catabolism serve regulatory and protective functions. Previous studies have shown that hypoxia induces HO-1 expression in cardiac myocytes. Accordingly, we investigated whether hypoxia-induced HO-1 expression is accompanied by increased CO production in cultured neonatal rat cardiac myocytes, and whether protein kinase C (PKC) is involved in hypoxia induced HO-1 gene expression.

METHODS AND RESULTS:

Expression of HO-1 in hypoxia-treated cells was examined by using northern and western blotting, and immunofluorescent staining. The level of HO-1 mRNA at 24 and 48 h was increased after the onset of hypoxia, with corresponding increase in the HO-1 protein level (6.7- and 8.7-fold at 24 and 48 h of hypoxia, respectively). HO-1 protein was colocalised with sarcomeric alpha-actin in hypoxic myocytes. Hypoxia also significantly increased the production of CO by 2.5- and 8-fold at 24 and 48 h, respectively. Under normoxic conditions, activation of PKC by phorbol-12-myristate-13-acetate (PMA; 100 nmol/L) markedly increased HO-1 gene expression, while inhibition of PKC activity by calphostin C (100 nmol/L) blocked hypoxia-induced HO-1 gene expression in cardiac myocytes.

CONCLUSIONS:

These results demonstrate that hypoxia markedly induces HO-1 expression and increases the production of CO in cardiac myocytes. This hypoxic response is attributed, at least in part, to activation of PKC. Increased HO-1 expression and resultant CO production may be beneficial with respect to protection of cardiac myocytes under hypoxic conditions.

• Authors: X Long, G Wu, D J Rozanski, M O Boluyt, M T Crow, E G Lakatta
• Journal: Heart, lung & circulation (Heart Lung Circ) Vol. 10 Issue 3 Pg. 121-9 ( 2001) ISSN: 1443-9506 [Print] Australia
• PMID: 16352050 (Publication Type: Journal Article)