期刊
PROTEOMICS
卷 12, 期 3, 页码 477-489出版社
WILEY
DOI: 10.1002/pmic.201100055
关键词
Animal proteomics; Chromium; Hepatotoxicity; MetaCore (TM); Misfolded proteins
资金
- National Science Council of Taiwan [NSC-99-2320-B-182-015-MY3]
- Chang Gung Memorial Hospital [CMRPD190201]
Chromium compounds are known to be associated with cytotoxicity and carcinogenicity when applied via the skin. However, there is no perspective research to elucidate the causations between chromium exposure and hepatotoxicity. In the present study, the impact of hexavalent/trivalent chromium on the liver and the underlying pathogenic processes were revealed in the female nude mice model. The liver damage under different treatments was evaluated by histologic examination. Functional proteome tools combined with a network analysis revealed statistically significant candidate protein networks predicted to be changed in the presence of chromium compounds. RNA interference-mediated silencing and immunohistochemistry were used to confirm whether the candidate protein was capable of resulting in hepatotoxicity elicited by chromium. Potassium chromate as the Cr(VI) compound generated greater oxidative stress, apoptosis and hepatotoxicity compared to chromium nitrate [Cr(III)]-treated samples. The most meaningful changes were observed amongst proteins involved in carbohydrate metabolism, endoplasmic reticulum (ER) stress, calcium homeostasis and apoptosis. Furthermore, abrogation of transitional ER ATPase (VCP) led to significant inhibition in hepatic cell viability under Cr(VI) administration, and the expression profiles of cytokeratin were closely correlated with apoptotic degrees of liver tissue. Collectively, our findings suggest that Cr(VI) might induce the accumulation of misfolded proteins and adverse effects leading to cell apoptosis and liver injury. These signature networks represent an approach to discover novel relationships in complex data, and functional proteomics of liver may provide solid evidence of chromium-caused hepatic damage via the skin.
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