title: Microcystin-LR induces apoptosis via NF-κB/iNOS pathway in INS-1 cells.
abstract: Cyanobacterial toxins, especially the microcystins, are found in eutrophied waters throughout the world, and their potential to impact on human and animal health is a cause for concern. Microcystin-LR (MC-LR) is one of the common toxic microcystin congeners and occurs frequently in diverse water systems. Recent work suggested that apoptosis plays a major role in the toxic effects induced by MC-LR in hepatocytes. However, the roles of MC-LR in pancreatic beta cells have not been fully established. The aim of the present study was to assess possible in vitro effects of MC-LR on cell apoptosis in the rat insulinoma cell line, INS-1. Our results demonstrated that MC-LR promoted selectively activation of NF-κB (increasing nuclear p50/p65 translocation) and increased the mRNA and protein levels of induced nitric oxide synthase (iNOS). The chronic treatment with MC-LR stimulated nitric oxide (NO) production derived from iNOS and induced apoptosis in a dose dependent manner in INS-1 cells. Meanwhile, this effect was inhibited by the NF-κB inhibitor PDTC, which reversed the apoptosis induced by MC-LR. Our observations indicate that MC-LR induced cell apoptosis via an iNOS-dependent pathway. A well-known nuclear transcription factor, NF-κB, is activated and mediates intracellular nitric oxide synthesis. We suggest that the apoptosis induced by chronic MC-LR in vivo presents a possible cause of β-cell dysfunction, as a key environmental factor in the development of diabetes mellitus.
authors.affiliation: Department of Cardiothoracic Surgery, The Affiliated Jiangyin People's Hospital of Southeast University Medical College, No.163 Shoushan Road, Jiangyin 214400, Jiangsu, China; E-Mails: ga1984ag@126.com (Y.J.); GuoQiangChen_nj@163.com (G.C.); BinHuang_nj@yeah.net (B.H.); XianZhang_nj@126.com (X.Z.); KaiShen_nj@126.com (K.S.).
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
authors.forename: Gao
authors.initials: G
authors.lastname: Lu
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.forename: Song
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D016328:NF-kappa B; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; C057862:cyanoginosin LR