Stress Signaling Pathways Regulated by Chromium Compounds

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CONFERENCE: Posters-at-the-Capitol

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Kelly, Amber; McCorkle, Ashley; Feil, Marilyn
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Chromium (VI) compounds are primarily produced for their industrial use in wood preservation, leather tanning, paint pigments and metallurgical products such as stainless steel. Chromium (VI) can readily enter cells and is quickly converted to chromium (III), thus acting as an oxidative agent. Interestingly, chromium (III) has been shown to sensitize insulin signaling and modulate fatty acid and carbohydrate metabolism. While chromium (VI) is a known inhaled carcinogen and its harmful effects are mediated through oxidative stress, the exact molecular mechanisms and cellular/metabolic effects of chromium (VI) have yet to be elucidated. In our studies, treatment of HepG2 cells with chromium (VI) resulted in cell death in a dose dependent manner. We further demonstrated that the treated cells underwent apoptosis, as evidenced by Poly ADP Ribose Polymerase (PARP) cleavage. Immunoblot analysis also suggested the activation of multiple pathways by chromium (VI) exposure. However, we could not detect observable changes in the levels of several metabolic enzymes involved in fat and carbohydrate metabolism. Our current studies involve using siRNAs and pharmacological inhibitors against metabolic enzymes to test whether they mediate the effects of chromium compounds.