Regulation of gadd153 mRNA expression by hypoxia in pulmonary artery smooth muscle cells

Hypoxia causes pulmonary hypertension and induces oxygen radicals in pulmon ary artery smooth muscle cells (PASMCs). Since oxidative stress regulates g add153 expression, we examined gadd153 mRNA in PASMCs cultured in a hypoxic environment. Gadd153 mRNA content was increased in PASMCs cultured for 24 hours in 1% oxygen. This increase was not abrogated by inhibition of protei n synthesis. To explore the signaling pathways mediating hypoxic regulation of gadd153 mRNA, the impact of calcium channel blockade by verapamil, G pr otein inhibition by pertussis toxin, and protein kinase C (PKC) down-regula tion, was examined. Although none of these interventions reduced basal expr ession of gadd153 mRNA in PASMCs, all of them suppressed the induction by h ypoxia. In contrast, antioxidants had no effect. These observations indicat e hypoxia induces gaddl53 expression in PASMCs through common signaling pat hways.