Oxidative Stress Increases RGS2 Expression which Suppresses Increased cAMP Accumulation in Response to CRF Activation in CATH.a Cells

Abstract

Regulator of G‐protein Signaling Protein (RGS)‐2 has been suggested as a modulator of anxiety and dysregulation of oxidative stress is implicated in the development of anxiety. In the present study, we report that hydrogen peroxide‐induced oxidative stress increases RGS2 expression and increases nuclear translocation of RGS2 in CATH.a cells. CATH.a cells express CRF1 receptors and RGS2 and are a model of locus coeruleus neurons. It is well known that stress causes excessive CRF1 receptor activation, increased cAMP production and increased locus coeruleus firing. We have observed that the cAMP response to CRF1 receptor activation is reduced by chronic hydrogen peroxide treatment in CATH.a cells. This reduced cAMP response may be the result of direct inhibition of adenylyl cyclase by RGS2 in response to oxidative stress. In addition, expression of antioxidant proteins including superoxide dismutase and heme oxygenase are also increased in response to increased oxidative stress. In conclusion, we hypothesize that the hydrogen peroxide treatment increases RGS2 expression as part of a compensatory mechanism to protect against oxidative stress. This protection is via two mechanisms; 1) increasing the expression of antioxidant proteins, and 2) direct inhibition of adenylyl cyclase to reduce cAMP accumulation caused by excessive CRF1 receptor activation. (Supported by NARSAD and NIH grant #GM060419).