Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 100, Issue 4, Pages 815-823Publisher
WILEY-BLACKWELL
DOI: 10.1002/jcb.21138
Keywords
rnitochondria; siRNA; apoptotic signaling kinase-1; EC-SOD; superoxide
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Funding
- NHLBI NIH HHS [HL34300, HL55601] Funding Source: Medline
- NIDDK NIH HHS [DK068134] Funding Source: Medline
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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 initochondrial 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.
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