Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop

doi:10.3390/nu14071504

	Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop
	Tang, Hengfang 1,2; Zheng, Zhiming 1; Wang, Han 1; Wang, Li 1; Zhao, Genhai 1; Wang, Peng 3,4
刊名	NUTRIENTS
	2022-04-01
卷号	14
关键词	vitamin K2 apoptosis ROS mitochondrial dysfunction mitophagy mitochondrial biogenesis mitochondrial quality-control loop PINK1 Parkin signaling pathway
DOI	10.3390/nu14071504
通讯作者	Zheng, Zhiming(zhengzhiming2014@163.com) ; Wang, Peng(pengwang@ipp.ac.cn)
英文摘要	Vitamin K2, a natural fat-soluble vitamin, is a potent neuroprotective molecule, owing to its antioxidant effect, but its mechanism has not been fully elucidated. Therefore, we stimulated SH-SY5Y cells with 6-hydroxydopamine (6-OHDA) in a proper dose-dependent manner, followed by a treatment of vitamin K2. In the presence of 6-OHDA, cell viability was reduced, the mitochondrial membrane potential was decreased, and the accumulation of reactive oxygen species (ROS) was increased. Moreover, the treatment of 6-OHDA promoted mitochondria-mediated apoptosis and abnormal mitochondrial fission and fusion. However, vitamin K2 significantly suppressed 6-OHDA-induced changes. Vitamin K2 played a significant part in apoptosis by upregulating and downregulating Bcl-2 and Bax protein expressions, respectively, which inhibited mitochondrial depolarization, and ROS accumulation to maintain mitochondrial structure and functional stabilities. Additionally, vitamin K2 significantly inhibited the 6-OHDA-induced downregulation of the MFN1/2 level and upregulation of the DRP1 level, respectively, and this enabled cells to maintain the dynamic balance of mitochondrial fusion and fission. Furthermore, vitamin K2 treatments downregulated the expression level of p62 and upregulated the expression level of LC3A in 6-OHDA-treated cells via the PINK1/Parkin signaling pathway, thereby promoting mitophagy. Moreover, it induced mitochondrial biogenesis in 6-OHDA damaged cells by promoting the expression of PGC-1 alpha, NRF1, and TFAM. These indicated that vitamin K2 can release mitochondrial damage, and that this effect is related to the participation of vitamin K2 in the regulation of the mitochondrial quality-control loop, through the maintenance of the mitochondrial quality-control system, and repair mitochondrial dysfunction, thereby alleviating neuronal cell death mediated by mitochondrial damage.
资助项目	Major Projects of Science and Technology of Anhui Province[202103a06020003] ; China National Key Research and Development Program[2019YFA0904300] ; China National Key Research and Development Program[2019YFA0904304] ; Key Research and Development Plan of Anhui Province[1804b06020342] ; Natural Science Foundation of Anhui Province[1908085MB48] ; Natural Science Foundation of Anhui Province[1908085MB43] ; National Natural Science Foundation of China[32070088]
WOS关键词	OXIDATIVE STRESS ; PARKINSONS ; MITOPHAGY ; PINK1 ; MECHANISMS ; AUTOPHAGY ; DYNAMICS ; PROTECTS ; MODELS ; ROLES
WOS研究方向	Nutrition & Dietetics
语种	英语
出版者	MDPI
WOS记录号	WOS:000782044500001
资助机构	Major Projects of Science and Technology of Anhui Province ; China National Key Research and Development Program ; Key Research and Development Plan of Anhui Province ; Natural Science Foundation of Anhui Province ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/128683]
专题	中国科学院合肥物质科学研究院
通讯作者	Zheng, Zhiming; Wang, Peng
作者单位	1.Chinese Acad Sci, Hefei Inst Phys Sci, Inst Intelligent Machines, Hefei 230031, Peoples R China 2.Univ Sci & Technol China, Sci Isl Branch Grad, Hefei 230026, Peoples R China 3.Chinese Acad Sci, Hefei Inst Phys Sci, Anhui Key Lab Environm Toxicol & Pollut Control T, Hefei 230031, Peoples R China 4.CAS Hefei Inst Technol Innovat Co Ltd, Hefei 230088, Peoples R China
推荐引用方式 GB/T 7714	Tang, Hengfang,Zheng, Zhiming,Wang, Han,et al. Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop[J]. NUTRIENTS,2022,14.
APA	Tang, Hengfang,Zheng, Zhiming,Wang, Han,Wang, Li,Zhao, Genhai,&Wang, Peng.(2022).Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop.NUTRIENTS,14.
MLA	Tang, Hengfang,et al."Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop".NUTRIENTS 14(2022).