Increased basal antioxidant levels in RCAN1 – deficient mice lowers oxidative injury after acute paraquat insult

Abstract

RCAN1 is an inhibitor of the phosphatase calcineurin, which is involved in the regulation of oxidative stress and apoptosis, among other important cell processes. Here we have used RCAN1 deficient mice (RCAN1-/-) to elucidate its role after an acute oxidative insult such as paraquat injection. We have observed that RCAN1-/- mice show less oxidative damage than wildtype (WT) mice after treatment. Under basal conditions, RCAN1-/- animals express more calcineurin, heme oxygenase-1, Nrf2, and catalase compared to WT mice (controls). This may explain the less severe effect of paraquat treatment on RCAN1-/- mice compared to WT. We showed that oxidative stress is involved in the early stages of apoptosis, thus we determined the apoptotic effector BAD and found that decreases in RCAN1-/- mice after treatment with paraquat compared with WT in similar experimental conditions. Our results suggest that RCAN1 may be involved in the balance between oxidant and antioxidant species production in vivo.