Regulation of cytochrome P4501A by protein kinase C: the role of heat shock protein70

Abstract

Carbofuran is a pesticide, which is used throughout the world as a nematicide and an acaricide. This pesticide integrates into living organisms through aquatic ecosystem. In earlier report, we had demonstrated that cytochrome P4501A was induced in cultured catfish hepatocytes in response to carbofuran, which might be responsible for the detoxification of this pesticide. As the underlying signaling mechanism associated with induction and regulation of cytochrome P4501A has not yet been well defined, we therefore in the present study have investigated to identify the regulatory network of cytochrome P4501A in catfish liver or cultured hepatocytes by targeting several key signaling molecules such as phosphatidyl inositol (PI) or protein kinase C (PKC), which are critical molecules for many important pathways. PKC and heat shock protein70 (HSP70) have been shown to be induced in response to carbofuran in catfish hepatocytes. Results also indicate that induction of CYP1A is modulated by HSP70 and PKC in fish hepatocytes. Thus our data shed light on the regulation of EROD activity, which has been used as a bio-monitoring tool for measuring aquatic pollution.