Carbon Monoxide Potentiation of L-Type Ca

The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway induced in astrocytes after ischemic brain injury promotes vascular endothelial growth factor (VEGF) expression to maintain and repair neurovascular function. Although HO-1-derived CO has been shown to induce hypoxia-inducible factor-1α (HIF-1α)-dependent VEGF expression, the underlying mechanism independent of HIF-1α remains to be elucidated.HO-1 and VEGF were coexpressed in astrocytes of ischemic mouse brain tissues. Experiments with specific siRNAs and pharmacological activators/inhibitors of various target genes demonstrated that astrocytes pre-exposed to the CO-releasing compound, CORM-2, or transfected with HO-1 increased HIF-1α-independent VEGF expression via sequential activation of the following signal cascades; CaHO-1-derived CO elicits CaOur results provide new mechanistic insight into the possible role for L-type Ca