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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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.