气候变化领域集成服务门户(CCPortal): Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B

CCPortal

DOI	10.1073/pnas.2020695118
	Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B
	Nagpal L.; Kornberg M.D.; Albacarys L.K.; Snyder S.H.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	Inositol hexakisphosphate kinases (IP6Ks) regulate various biological processes. IP6Ks convert IP6 to pyrophosphates such as diphosphoinositol pentakisphosphate (IP7) and bis-diphosphoinositol tetrakisphosphate (IP8). IP7 is produced in mammals by a family of inositol hexakisphosphate kinases, IP6K1, IP6K2, and IP6K3, which have distinct biological functions. The inositol hexakisphosphate kinase 2 (IP6K2) controls cellular apoptosis. To explore roles for IP6K2 in brain function, we elucidated its protein interactome in mouse brain revealing a robust association of IP6K2 with creatine kinase-B (CK-B), a key enzyme in energy homeostasis. Cerebella of IP6K2-deleted mice (IP6K2-knockout [KO]) produced less phosphocreatine and ATP and generated higher levels of reactive oxygen species and protein oxidative damage. In IP6K2-KO mice, mitochondrial dysfunction was associated with impaired expression of the cytochrome-c1 subunit of complex III of the electron transport chain. We reversed some of these effects by combined treatment with N-acetylcysteine and phosphocreatine. These findings establish a role for IP6K2-CK-B interaction in energy homeostasis associated with neuroprotection. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Creatine kinase; Electron transport chain; Inositol phosphates; Mitochondrial dysfunction; Oxidative stress
语种	英语
scopus关键词	acetylcysteine; creatine kinase; creatine kinase B; creatine phosphate; cytochrome c1; inositol hexakisphosphate kinase 2; pyrophosphate; reactive oxygen metabolite; unclassified drug; animal experiment; animal tissue; apoptosis; Article; brain function; cell function; controlled study; electron transport; enzyme regulation; female; homeostasis; male; mouse; neuroprotection; nonhuman; oxidative stress; priority journal; protein expression; protein protein interaction
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180732
作者单位	The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
推荐引用方式 GB/T 7714	Nagpal L.,Kornberg M.D.,Albacarys L.K.,et al. Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B[J],2021,118(6).
APA	Nagpal L.,Kornberg M.D.,Albacarys L.K.,&Snyder S.H..(2021).Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Nagpal L.,et al."Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).