Hypoxia-induced haem oxygenase-1 gene expression in neonatal rat cardiac myocytes

Xilin Long, Guimei Wu, Dennis J. Rozanski, Marvin O. Boluyt, Michael T. Crow, Edward G. Lakatta

Research output: Contribution to journalArticlepeer-review

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 α-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.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalHeart Lung and Circulation
Volume10
Issue number3
DOIs
StatePublished - Jan 1 2001

Keywords

  • Carbon monoxide
  • Haem oxygenase
  • Hypoxia
  • Myocytes
  • Protein kinase C

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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