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

Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System.
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DOI:
10.3390/ijms23137041
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发表时间:
2022-06-24
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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血红素加氧酶 (HO) 通过其代谢物(包括一氧化碳 (CO)、胆绿素或胆红素和二价铁)既有有益作用,也有有害作用。 HO-1 是 HO 的诱导形式,氧化应激、一氧化氮、CO 和缺氧会上调,而 HO-2 是调节血管张力和稳态的组成形式。在因创伤、缺血再灌注或阿尔茨海默病 (AD) 损伤的大脑中,可以检测到 HO-1 的长期表达,这可以通过铁积累导致细胞毒性铁死亡。相比之下,损伤周围区域短暂诱导 HO-1 可能具有再生潜力(例如血管生成、神经发生和线粒体生物发生),并通过 CO 介导的信号通路、胆红素的抗氧化特性和铁介导的铁蛋白合成发挥神经血管保护作用。在这篇综述中,我们讨论了 HO-1 及其代谢物在各种神经血管疾病中的双重作用,包括年龄相关性黄斑变性、缺血再灌注损伤、创伤性脑损伤、吉尔伯特综合征和 AD。
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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