Microcystin-LR Induces Apoptosis via NF-κB /iNOS Pathway in INS-1 Cells

International Journal of Molecular Sciences

Yong Ji¹  Gao Lu²  Guoqiang Chen¹  Bin Huang¹  Xian Zhang¹  Kai Shen¹ 

[1] 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:;Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 210029, Jiangsu, China; E-Mail:

关键词: INS-1;    NF-κB;    iNOS;    Microcystin-LR;    apoptosis;   

DOI  :  10.3390/ijms12074722

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2011 by the authors; licensee MDPI, Basel, Switzerland.