期刊
TOXICOLOGY IN VITRO
卷 28, 期 2, 页码 307-318出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2013.11.011
关键词
Cadmium; SK-RC-45 cell line; NICE cell line; Oxidative stress; Antioxidative defense; HO-1; JNK dependent and independent apoptosis; Intrinsic and extrinsic apoptotic pathways
类别
资金
- Indian Council of Medical Research (ICMR)
Cadmium (Cd2+) is a major nephrotoxic environmental pollutant, affecting mostly proximal convoluted tubule (PCT) cells of the mammalian kidney, while conditionally Cd2+ could also elicit protective responses with great variety and variability in different systems. The present study was designed to evaluate the molecular mechanism of Cd2+ toxicity on human PCT derived Renal Cell Carcinoma (RCC), SK-RC-45 and compare its responses with normal human PCT derived cell line, NICE. Exposure of SK-RC-45 cells with different concentrations of CdCl2 (e.g. 0,10 and 20 mu M) in serum free medium for 24 h generate considerable amount of ROS, accompanied with decreased cell viability and alternations in the cellular and nuclear morphologies, heat shock responses and GCLC mediated protective responses. Also phosphatidylserine externalization, augmentation in the level of caspase-3, PARP, BAD, Apafl and cleaved caspase-9 along with decreased expression of Bcl2 and release of cytochrome c confirmed that, Cd2+ dose dependently induces solely intrinsic pathway of apoptosis in SK-RC-45, independent of JNK. Furthermore, the non-toxic concentration (10 mu M) of Cd2+ induced nuclear translocation of Nrf2 and increased expression in the level of HO-1 enzyme suggesting that at the milder concentration, Cd2+ induces protective signaling pathways. On the other hand, exposure of NICE to different concentrations of CdC12 (e.g. 0, 10, 20, 30 and 50 mu M) under the same conditions elevate stronger heat shock and SOD2 mediated protective responses. In contrary to the RCC PCT, the normal PCT derived cell follows JNK dependent and extrinsic pathways of apoptosis. Cumulatively, these results suggest that Cd2+ exposure dose dependently elicit both cell proliferative and cell death related responses in SK-RC-45 cells and is differentially regulated with respect to normal kidney epithelia derived NICE cells. (C) 2013 Elsevier Ltd. All rights reserved.
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