PMID- 20708680
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20210319
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 49
IP  - 10
DP  - 2010 Nov 30
TI  - Dysfunctional Nrf2-Keap1 redox signaling in skeletal muscle of the sedentary old.
PG  - 1487-93
LID - 10.1016/j.freeradbiomed.2010.08.010 [doi]
AB  - The role of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and Kelch-like 
      ECH-associated protein 1 (Keap1) redox signaling has not been characterized in 
      human skeletal muscle despite an extensive delineation of oxidative stress in the 
      etiology of aging and sarcopenia. We assessed whether the age-associated decline 
      in antioxidant response is due, at least in part, to dysfunction in Nrf2-Keap1 
      redox signaling. We also evaluated whether an active lifestyle can conserve 
      skeletal muscle cellular redox status via activation of Nrf2-Keap1 signaling. 
      Here we show that a recreationally active lifestyle is associated with the 
      activation of upstream modulators that induce the Nrf2-mediated antioxidant 
      response cascade in skeletal muscle of the elderly. Conversely, a sedentary 
      lifestyle is negatively associated with these adaptations mainly because of 
      dysregulation of Nrf2-Keap1 redox signaling that renders the intracellular 
      environment prone to reactive oxygen species-mediated toxicity. Our results 
      indicate that an active lifestyle is an important determinant of cellular redox 
      status. We propose that the metabolic induction of Nrf2-Keap1 redox signaling 
      promises to be a viable therapy for attenuating oxidative stress-mediated damage 
      in skeletal muscle associated with physical inactivity.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Safdar, Adeel
AU  - Safdar A
AD  - Department of Kinesiology, McMaster University, Hamilton, ON L8N 3Z5, Canada.
FAU - deBeer, Justin
AU  - deBeer J
FAU - Tarnopolsky, Mark A
AU  - Tarnopolsky MA
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100811
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (KEAP1 protein, human)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cell Line
MH  - Female
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*physiology
MH  - Kelch-Like ECH-Associated Protein 1
MH  - Lipid Peroxidation
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Muscle, Skeletal/*metabolism
MH  - NF-E2-Related Factor 2/*physiology
MH  - Osteoarthritis, Knee/physiopathology
MH  - Oxidation-Reduction
MH  - *Sedentary Behavior
MH  - Signal Transduction/*physiology
EDAT- 2010/08/17 06:00
MHDA- 2011/02/18 06:00
CRDT- 2010/08/17 06:00
PHST- 2010/01/28 00:00 [received]
PHST- 2010/06/15 00:00 [revised]
PHST- 2010/08/04 00:00 [accepted]
PHST- 2010/08/17 06:00 [entrez]
PHST- 2010/08/17 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
AID - S0891-5849(10)00478-8 [pii]
AID - 10.1016/j.freeradbiomed.2010.08.010 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2010 Nov 30;49(10):1487-93. doi: 
      10.1016/j.freeradbiomed.2010.08.010. Epub 2010 Aug 11.