Abstract
The contribution of heme oxygenase HO‐2, the primary source of bilirubin and carbon monoxide (CO) under physiological conditions, to the regulation of vascular function has remained largely unexplored. Using siRNA HO‐2, we examined the effect of suppressed levels of HO‐2 on vascular antioxidant and survival proteins. In vivo HO‐2 siRNA treatment decreased the basal levels of EC‐SOD, pAKT proteins (serine‐473 and threonine‐308), without changing Akt protein expression. HO‐2 siRNA treatment increased 3‐nitrotyrosine (3‐NT) and apoptotic signaling kinase‐1 (ASK‐1) (P < 0.01). HO activity was decreased by the use of siRNA HO‐2. We extended these studies to the mitochondria, examining for the presence of HO‐1 and its role in the regulation of pro‐ and anti‐apoptotic proteins. HO activity was increased by the administration of CoPP resulting in the translocation of HO‐1 into the mitochondria, mainly to the inner face of the mitochondrial inner membrane. These findings suggest that HO‐2 is critical in the maintenance of heme homeostasis and also the regulation of apoptosis by controlling levels of EC‐SOD, Akt, 3‐NT, and ASK‐1. In addition, localization of HO‐1 in the mitochondrial compartment plays a critical role in mitochondria‐mediated apoptosis. J. Cell. Biochem. 100: 815–823, 2007. © 2006 Wiley‐Liss, Inc.