Paradoxical roles of antioxidant enzymes: Basic mechanisms and health implications.

doi:10.1152/physrev.00010.2014

科研成果详情

题名	Paradoxical roles of antioxidant enzymes: Basic mechanisms and health implications.
作者	Xin Gen Lei; Jian-Hong Zhu; Wen-Hsing Cheng; Yongping Bao; Ye-Shih Ho; Amit R Reddi; Arne Holmgren; Elias S J Arnér
发表期刊	Physiol Rev. 影响因子和分区
语种	英语
原始文献类型	Review
其他关键词	EXTRACELLULAR-SUPEROXIDE-DISMUTASE ; CELLULAR GLUTATHIONE-PEROXIDASE ; MITOCHONDRIAL THIOREDOXIN REDUCTASE ; SELENOCYSTEINE TRANSFER-RNA ; CARDIAC-SPECIFIC OVEREXPRESSION ; EARLY EMBRYONIC LETHALITY ; TUMOR-NECROSIS-FACTOR ; METHIONINE SULFOXIDE REDUCTASE ; AMYOTROPHIC-LATERAL-SCLEROSIS ; PROTEIN-TYROSINE PHOSPHATASES
摘要	Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate paradoxical outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of antioxidant nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that paradoxical roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways.
资助项目	National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK 53018]; Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [31320103920]; NSFCNational Natural Science Foundation of China (NSFC) [31201065, 31310103026]; Zhejiang Provincial Natural Science Fund for Distinguished Young Scholars [LR13H020002]; Cancer Prevention Research Trust, UK; National Institute of Environmental Health Sciences of the NIH [R21ES025661]; Georgia Institute of Technology; Swedish Research CouncilSwedish Research CouncilEuropean Commission; Swedish Cancer SocietySwedish Cancer Society; Karolinska InstitutetKarolinska Institutet; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK053018] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [R21ES025661] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R21AG055022] Funding Source: NIH RePORTER
出版者	AMER PHYSIOLOGICAL SOC
出版地	BETHESDA
ISSN	0031-9333
EISSN	1522-1210
卷号	96 期号:1 页码:307-364
DOI	10.1152/physrev.00010.2014
WOS类目	Physiology
WOS研究方向	Physiology
WOS记录号	WOS:000370383200009
收录类别	SCIE ; PUBMED ; SCOPUS
发表日期	2016-01
URL	查看原文
Pubmed记录号	26681794
PMC记录号	PMC4839492
Scopus记录号	2-s2.0-84950153936
ESI高被引论文	2024-05
自科自定义期刊分类	T2(B)类
引用统计	被引频次：192[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/155880
专题	公共卫生与管理学院_预防医学系
通讯作者	Xin Gen Lei
作者单位	Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou
第一作者单位	温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Xin Gen Lei,Jian-Hong Zhu,Wen-Hsing Cheng,et al. Paradoxical roles of antioxidant enzymes: Basic mechanisms and health implications.[J]. Physiol Rev.,2016,96(1):307-364.
APA	Xin Gen Lei., Jian-Hong Zhu., Wen-Hsing Cheng., Yongping Bao., Ye-Shih Ho., ... & Elias S J Arnér. (2016). Paradoxical roles of antioxidant enzymes: Basic mechanisms and health implications.. Physiol Rev., 96(1), 307-364.
MLA	Xin Gen Lei,et al."Paradoxical roles of antioxidant enzymes: Basic mechanisms and health implications.".Physiol Rev. 96.1(2016):307-364.