Post-translational modifications in cerebral ischemia-reperfusion

doi:10.11817/j.issn.1673-9248.2022.02.012

Abstract

Abstract:

Post-translational modifications of proteins refer to the covalent processing in translation or post-translation, which can alter the structure and function of the proteins. Post-translational modifications are essential to maintain cellular function and cellular environmental homeostasis. In cerebral ischemia-reperfusion, post-translation modifications regulate many processes, including metabolism, oxidative stress, apoptosis and axon growth. This review mainly focuses on three common types of post-translational modifications: phosphorylation, ubiquitylation and acetylation. We summarize the impacts of these modifications during the cerebral ischemia-reperfusion injury and crosstalk among these modifications which may give us hints about the effective targets for ischemic stroke.

Key words: Cerebral ischemia-reperfusion injury, Post-translational Modification, Phosphorylation, Ubiquitylation, Acetylation

Zexuan Hong, Tao Tao, Zaisheng Qin. Post-translational modifications in cerebral ischemia-reperfusion[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2022, 16(02): 125-129.

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PTM类型	蛋白	作用机制	参考文献
磷酸化	闭合蛋白	增加血管通透性	[7]
	Tie-2	抑制血管通透性	[8]
	JAK2、STAT3、NMDAR	促进Bcl-2、Bcl-xL、TIMP-1、Btg2等抗凋亡蛋白转录；增加活性氧产生	[9, 10]
	AMPK	抑制NF-κB、IL-6、IL-1β、TNF-α，上调HO-1和谷胱甘肽	[11]
	STAT3	促进小胶质细胞向M2型转化	[10]
泛素化	MFN2	线粒体结构破坏，影响胞内ATP合成、凋亡、活性氧及钙稳态	[19, 20]
	Rac1	激活NF-κB相关的炎症通路及Nox2介导的氧化应激反应	[21]
	HIF-1α	上调iNOS、VEGF、HO-1、LDH-A、PFK-L、PKM、ALD-A等分子	[23-25]
	Nrf2	促进下游抗氧化基因如HO-1、活性氧的转录	[27]
乙酰化	组蛋白4	促进组织再生及轴突生长	[35]
	p53	上调PUMA、Bax，导致细胞色素C的释放及caspase-3的激活	[43-46]
	SOD2	抗氧化功能抑制，使线粒体中活性氧产生增加	[48-49]
	组蛋白3	促进神经细胞凋亡	[34]

PTM类型	蛋白	作用机制	参考文献
磷酸化	闭合蛋白	增加血管通透性	[7]
	Tie-2	抑制血管通透性	[8]
	JAK2、STAT3、NMDAR	促进Bcl-2、Bcl-xL、TIMP-1、Btg2等抗凋亡蛋白转录；增加活性氧产生	[9, 10]
	AMPK	抑制NF-κB、IL-6、IL-1β、TNF-α，上调HO-1和谷胱甘肽	[11]
	STAT3	促进小胶质细胞向M2型转化	[10]
泛素化	MFN2	线粒体结构破坏，影响胞内ATP合成、凋亡、活性氧及钙稳态	[19, 20]
	Rac1	激活NF-κB相关的炎症通路及Nox2介导的氧化应激反应	[21]
	HIF-1α	上调iNOS、VEGF、HO-1、LDH-A、PFK-L、PKM、ALD-A等分子	[23-25]
	Nrf2	促进下游抗氧化基因如HO-1、活性氧的转录	[27]
乙酰化	组蛋白4	促进组织再生及轴突生长	[35]
	p53	上调PUMA、Bax，导致细胞色素C的释放及caspase-3的激活	[43-46]
	SOD2	抗氧化功能抑制，使线粒体中活性氧产生增加	[48-49]
	组蛋白3	促进神经细胞凋亡	[34]

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