Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System

被引:39
作者
Choi, Yoon Kyung [1 ]
Kim, Young-Myeong [2 ]
机构
[1] Konkuk Univ, Dept Biosci & Biotechnol, Bio Mol Informat Ctr, Seoul 05029, South Korea
[2] Kangwon Natl Univ, Sch Med, Dept Mol & Cellular Biochem, Chunchon 24341, South Korea
基金
新加坡国家研究基金会;
关键词
heme oxygenase; carbon monoxide; iron; bilirubin; ferroptosis; regeneration; HUMAN BILIVERDIN REDUCTASE; HYPOXIA-INDUCIBLE FACTORS; ACTIVATED PROTEIN-KINASE; TRAUMATIC BRAIN-INJURY; CARBON-MONOXIDE; NITRIC-OXIDE; MITOCHONDRIAL BIOGENESIS; OXIDATIVE STRESS; VEGF EXPRESSION; CA2+ CHANNELS;
D O I
10.3390/ijms23137041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Heme oxygenase (HO) has both beneficial and detrimental effects via its metabolites, including carbon monoxide (CO), biliverdin or bilirubin, and ferrous iron. HO-1 is an inducible form of HO that is upregulated by oxidative stress, nitric oxide, CO, and hypoxia, whereas HO-2 is a constitutive form that regulates vascular tone and homeostasis. In brains injured by trauma, ischemia-reperfusion, or Alzheimer's disease (AD), the long-term expression of HO-1 can be detected, which can lead to cytotoxic ferroptosis via iron accumulation. In contrast, the transient induction of HO-1 in the peri-injured region may have regenerative potential (e.g., angiogenesis, neurogenesis, and mitochondrial biogenesis) and neurovascular protective effects through the CO-mediated signaling pathway, the antioxidant properties of bilirubin, and the iron-mediated ferritin synthesis. In this review, we discuss the dual roles of HO-1 and its metabolites in various neurovascular diseases, including age-related macular degeneration, ischemia-reperfusion injury, traumatic brain injury, Gilbert's syndrome, and AD.
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页数:19
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