Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System |
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Authors: | Yoon Kyung Choi Young-Myeong Kim |
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Affiliation: | 1.Bio/Molecular Informatics Center, Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea;2.Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 24341, Korea |
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Abstract: | 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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Keywords: | heme oxygenase carbon monoxide iron bilirubin ferroptosis regeneration |
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