Pge1–Induced No Reduces Apoptosis by D–Galactosamine Through Attenuation of Nf–Kb and Nos–2 Expression in Rat Hepatocytes

Abstract

P rostaglandins are biologically active polyunsaturated fatty acids derived from arachidonic acid present in most mammalian tissues. 1 Prostaglandin E 1 (PGE 1 ) reduces liver injury induced experimentally 2 and in fulminant viral hepatitis in humans. 3 PGE 1 exerts most of its effects by promoting membrane stabilization, 4 , hepatocyte proliferation, 5 vasodilation, 6 and inhibition of fibrogenesis. 7 The preadministration of PGE 1 also reduces liver injury through the enhancement of inducible NO synthase (NOS-2) expression in hepatocytes. 8 Nevertheless, the detailed molecular mechanism through which PGE 1 regulates NOS-2 expression is not completely understood. It is clearly established that the effects of PGE result from its binding to its receptors, EP 1 , EP 2 , and EP 4 , all of which can stimulate the production of the second messenger cyclic 3Ј,5Ј adenosine monophosphate (cAMP). This messenger induces NOS-2 expression in numerous cell types, including vascular smooth

Nitric oxide mimics transcriptional and post-translational regulation during α-Tocopherol cytoprotection against glycochenodeoxycholate-induced cell death in hepatocytes

“…activation of soluble guanylate cyclase and inhibition of cytochrome c oxidase, or by producing covalent protein post-translational modifications, such as cysteine S-nitrosylation and tyrosine nitration, that can alter protein function [18]. NO has been shown to exert pro-apoptotic and anti-apoptotic effects in cultured hepatocytes [19][20][21]. GCDCA prevented NOS-2 expression and NO production in cytokine-treated rat hepatocytes [22].…”

Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice

“…According to this data, adiponectin inhibited hepatic NF-kB signaling in ConA-induced acute liver failure. Recent reports demonstrated that hepatoprotective and antiapoptotic molecules such as S-Adenosylmethionine and PGE1 may reduce NF-kB activation in hepatocytes [16,17]. However, further signaling pathways being involved in the anti-apoptotic effects of adiponectin in hepatocytes remain to be elucidated.…”

Homocysteine Induces Monocyte Chemoattractant Protein-1 Expression in Hepatocytes Mediated via Activator Protein-1 Activation

“…Hepatocytes were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum (Invitrogen). Hepatocytes were incubated for 24 h post-isolation before experiments (8,31).…”

“…Activation of both or either one of these transcription factors can elicit MCP-1 gene expression (27)(28)(29). Both AP-1 and NF-B are present in hepatocytes and can be activated in response to various stimuli (30,31). Hcy-induced MCP-1 expression in vascular smooth cells and monocytes/macrophages appears to be mediated via NF-B activation (29,32).…”