title: Heme oxygenase-1-mediated partial cytoprotective effect by NO on cadmium-induced cytotoxicity in C6 rat glioma cells.
abstract: Heme oxygenase-1 (HO-1) is a 32-kDa stress induced enzyme that degrades heme to carbon monoxide (CO) and biliverdin. By employing RT-PCR and Western blotting techniques, we have examined the HO-1 induction in C6 glioma cells that were treated with cadmium chloride (CdCl(2)) or spermine NONOate (SPER/NO). By employing a cell viability assay, we have also examined the cytoprotective effect of HO-1 induction against the cytotoxicity caused by toxic dose of CdCl(2). In C6 glioma cells exposed to CdCl(2), expression of HO-1 (mRNA and protein) was increased in a dose- and time-dependent manner. Nitric oxide (NO) generated from SPER/NO very rapidly increased HO-1 mRNA expression in the C6 glioma cells. The induction of HO-1 by SPER/NO protected the cells from toxic dose of CdCl(2). The up-regulation of HO-1 mRNA expression by CdCl(2) was inhibited by a pre-incubation of the cells with actinomycin D, a potent inhibitor of mRNA transcription. Upon the inhibition of elevated HO-1 mRNA expression by the use of zinc protoporphyrin IX (ZnPP), an inhibitor of HO activity, the change of HO-1 mRNA expression by ZnPP was not observed. Thus, the glial cell may respond to CdCl(2) toxicity by enhancing the HO-1 expression in its effort to minimize the CdCl(2)-derived oxidative damage, and to survive. In the glioma cells, when the HO-1 expression was elevated by a prior incubation with SPER/NO, the cell viability against the cytotoxicity of CdCl(2) was significantly increased. When the results of our experiment are taken together, we discovered that NO provided a rapid enhancement of HO-1 expression, and it provided a protective effect against CdCl(2)-derived oxidative injury in the C6 rat glioma cells.
authors.affiliation: Department of Pharmacology and Toxicology, College of Medicine, Inha University, 253 Yonghyun-dong, Nam-gu, Incheon 382-751, South Korea.
authors.forename: Klaokwan
authors.initials: K
authors.lastname: Srisook
authors.forename: Nam-Hee
authors.initials: NH
authors.lastname: Jung
authors.forename: Bum-Rae
authors.initials: BR
authors.lastname: Kim
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Cha
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Cha
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002104:Cadmium / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D009569:Nitric Oxide / Q000096:biosynthesis*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D011524:Protoporphyrins; D012333:RNA, Messenger; D002104:Cadmium; C091861:spermine nitric oxide complex; C017803:zinc protoporphyrin; D013096:Spermine; D009569:Nitric Oxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1