Understanding the Cytotoxicity of Hexavalent Chromium
Yinsheng Wang, Ph.D.
University of California, Riverside
NIEHS Grant R01ES019873
In a study funded in part by the NIEHS, researchers report that hexavalent chromium, or CR(VI), cytotoxicity may partially result from its up regulation of cholesterol biosynthesis. Cr(VI) is generated during industry processes and is carcinogenic. A better understanding of the mechanisms for the cytotoxicity of this heavy metal could be used to develop therapies that decrease health effects after exposure.
The researchers used stable isotope labeling by amino acids in cell culture (SILAC) coupled with tandem mass spectrometry to study the cellular mechanisms affected by Cr(VI). This quantitative proteomic technique revealed 4,607 unique proteins involved in Cr(VI) perturbation of cells. Of these, 270 proteins were significantly up regulated and 127 down regulated.
The researchers found that Cr(VI) affected cholesterol biosynthesis, G-protein signaling, inflammatory response, and selenoprotein pathways. Cells treated with Cr(VI) had much higher expression of a large number of enzymes involved in cholesterol biosynthesis, and multiple cell lines showed increases in cellular cholesterol levels. In addition, the cholesterol-lowering drug lovastatin reduced growth inhibition of cultured human cells brought on by Cr(VI).
Citation: Guo L, Xiao Y, Wang Y. 2013. Hexavalent Chromium-induced Alteration of Proteomic Landscape in Human Skin Fibroblast Cells. J Proteome Res 12(7):3511-3518.
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