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Int. J. Mol. Sci. 2011, 12(7), 4722-4734; doi:10.3390/ijms12074722
Article

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

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1 Department of Cardiothoracic Surgery, The Affiliated Jiangyin people’s Hospital of Southeast university medical college, No.163 Shoushan Road, Jiangyin 214400, Jiangsu, China 2 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 / Revised: 14 July 2011 / Accepted: 18 July 2011 / Published: 22 July 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 INS-1; NF-κB, iNOS; Microcystin-LR; apoptosis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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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.

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