首页|Modulation of PARP activity by Monomethylarsonous (MMA(+3)) acid and uranium in mouse thymus
Modulation of PARP activity by Monomethylarsonous (MMA(+3)) acid and uranium in mouse thymus
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NSTL
Elsevier
Arsenic exposure is well established to impair the function of zinc finger proteins, including PARP-1. Previous studies from our lab show that early developing T cells in the thymus are very sensitive to arsenite (As+3)-induced genotoxicity mediated through PARP-1 inhibition. Additionally, it has been shown that uranium (in the form of uranyl acetate, UA) also suppresses PARP-1 activity in HEK cells. However, very little is known about whether the As+3 metabolite, monomethylarsonous acid (MMA(+3)), also inhibits PARP-1 activity and if this is modified by combined exposures with other metals, such as uranium. In the present study, we found that MMA(+3) significantly suppressed PARP-1 function, whereas UA at high concentrations significantly increased PARP-1 activity. To evaluate whether the effects on PARP-1 activity were mediated through oxidative stress, we measured the induction of hemoxygenase-1 (Hmox-1) expression by qPCR. MMA(+3), but not UA, significantly induced oxidative stress; however, the inhibition of PARP-1 produced by MMA(+3) was not reversed by the addition of the antioxidant, Tempol. Further evaluation revealed minimal interactive effects of MMA(+3) and UA on PARP-1 function. Collectively, our results show that contrary to As+3, the suppressive effects of MMA(+3) on PARP-1 were not substantially driven by oxidative stress' in mouse thymus cells. Results for this study provide important insights into the effects of MMA(+3) and uranium exposures on PARP-1 function, which is essential for future studies focused on understanding the effects of complex environmentally relevant metal mixtures.
NSTL
Elsevier
