| dc.description.abstract | Sodium arsenite is a well-known carcinogen and may cause cardiovascular disease, such as atherosclerosis and blackfoot disease. Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes heme degradation into iron, biliverdin, and carbon monoxide. HO-1 is induced by a variety of agents, such as heme, oxidative stress, heat shock, UV irradiation, and some heavy metals (arsenite and cadmium). HO-1 has been proposed to play a dual role in protecting cells against or stimulating intracellular oxidative injury. We investigated the induction of HO-1 by low doses of sodium arsenite (< 1 micro mol/L) in bovine aortic endothelial cells (BAEC). Our results show that both HO-1 protein and mRNA are significantly induced by treatment of BAEC cells with 1mM sodium arsenite. To examine which pathway or which signaling molecule is involved in low dose sodium arsenite-mediated induction of HO-1, several enzyme inhibitors were adopted in this study. Among these inhibitors, protein kinase C (PKC) inhibitors such as H7, staurosporine, and chelerythrine chloride decreased 1 mM sodium arsenite-induced HO-1 expression, whereas inhibitors of tyrosine kinase, nitric oxide synthase (NOS), extracellular-regulated kinase (ERK), and PI-3 kinase are unable to inhibit HO-1 induction. Furthermore, the translocation of various PKC isoforms is then examined by histoimmunochemical technique. The present results have shown that PKC-eta and PKC-epsilon are apparently translocated from cytosol to membrane after 1 micro mol/L sodium arsenite treatment. Therefore PKC-eta and PKC-epsilon is probably involved in low dose sodium arsenite-indued HO-1 expression in BAEC. | en_US |