NDLI: Relationship of electrophilic stress to aging.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zimniak, Piotr
Description	Country affiliation: United States Author Affiliation: Zimniak P ( Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. zimniakpiotr@uams.edu)
Abstract	This review begins with the premise that an organism's life span is determined by the balance between two countervailing forces: (i) the sum of destabilizing effects and (ii) the sum of protective longevity-assurance processes. Against this backdrop, the role of electrophiles is discussed, both as destabilizing factors and as signals that induce protective responses. Because most biological macromolecules contain nucleophilic centers, electrophiles are particularly reactive and toxic in a biological context. The majority of cellular electrophiles are generated from polyunsaturated fatty acids by a peroxidation chain reaction that is readily triggered by oxygen-centered radicals, but propagates without further input of reactive oxygen species (ROS). Thus, the formation of lipid-derived electrophiles such as 4-hydroxynon-2-enal (4-HNE) is proposed to be relatively insensitive to the level of initiating ROS, but to depend mainly on the availability of peroxidation-susceptible fatty acids. This is consistent with numerous observations that life span is inversely correlated to membrane peroxidizability, and with the hypothesis that 4-HNE may constitute the mechanistic link between high susceptibility of membrane lipids to peroxidation and shortened life span. Experimental interventions that directly alter membrane composition (and thus their peroxidizability) or modulate 4-HNE levels have the expected effects on life span, establishing that the connection is not only correlative but causal. Specific molecular mechanisms are considered, by which 4-HNE could (i) destabilize biological systems via nontargeted reactions with cellular macromolecules and (ii) modulate signaling pathways that control longevity-assurance mechanisms.
File Format	HTM / HTML
ISSN	08915849
e-ISSN	18734596
DOI	10.1016/j.freeradbiomed.2011.05.039
Journal	Free Radical Biology and Medicine
Issue Number	6
Volume Number	51
Language	English
Publisher	Elsevier
Publisher Date	2011-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Free radicals biology Aging Physiology Oxidative Stress Aldehydes Metabolism Animals Lipid Peroxidation Reactive Oxygen Species Signal Transduction Research Support, N.i.h., Extramural Research Support, U.s. Gov't, Non-p.h.s.
Content Type	Text
Resource Type	Article
Subject	Physiology (medical) Biochemistry

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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