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Microcystin-LR Induces Apoptosis via NF-κB /iNOS Pathway in INS-1 Cells
Department of Cardiothoracic Surgery, The Affiliated Jiangyin people’s Hospital of Southeast university medical college, No.163 Shoushan Road, Jiangyin 214400, Jiangsu, China
Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 210029, Jiangsu, China
* Author to whom correspondence should be addressed.
Received: 15 June 2011; in revised form: 14 July 2011 / Accepted: 18 July 2011 / Published: 22 July 2011
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.
Keywords: INS-1; NF-κB, iNOS; Microcystin-LR; apoptosis
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MDPI and ACS Style
Ji, Y.; Lu, G.; Chen, G.; Huang, B.; Zhang, X.; Shen, K.; Wu, S. Microcystin-LR Induces Apoptosis via NF-κB /iNOS Pathway in INS-1 Cells. Int. J. Mol. Sci. 2011, 12, 4722-4734.
Ji Y, Lu G, Chen G, Huang B, Zhang X, Shen K, Wu S. Microcystin-LR Induces Apoptosis via NF-κB /iNOS Pathway in INS-1 Cells. International Journal of Molecular Sciences. 2011; 12(7):4722-4734.
Ji, Yong; Lu, Gao; Chen, Guoqiang; Huang, Bin; Zhang, Xian; Shen, Kai; Wu, Song. 2011. "Microcystin-LR Induces Apoptosis via NF-κB /iNOS Pathway in INS-1 Cells." Int. J. Mol. Sci. 12, no. 7: 4722-4734.