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PMID: 16186101 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Regulation of oxidative stress by the anti-aging hormone klotho.

The Journal of biological chemistry ·Vol. 280 ·No. 45 ·2005-11-11 ·Pages 38029-34

Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, Miyoshi M, Ogawa Y, Castrillon DH, Rosenblatt KP, Kuro-o M

Abstract

klotho is an aging suppressor gene and extends life span when overexpressed in mice. Klotho protein was recently demonstrated to function as a hormone that inhibits insulin/insulin-like growth factor-1 (IGF-1) signaling. Here we show that Klotho protein increases resistance to oxidative stress at the cellular and organismal level in mammals. Klotho protein activates the FoxO forkhead transcription factors that are negatively regulated by insulin/IGF-1 signaling, thereby inducing expression of manganese superoxide dismutase. This in turn facilitates removal of reactive oxygen species and confers oxidative stress resistance. Thus, Klotho-induced inhibition of insulin/IGF-1 signaling is associated with increased resistance to oxidative stress, which potentially contributes to the anti-aging properties of klotho.

MeSH Terms
8-Hydroxy-2'-Deoxyguanosine Animals Deoxyguanosine/analogs & derivatives,urine Forkhead Transcription Factors/metabolism Gene Deletion Glucuronidase HeLa Cells Humans Insulin/metabolism Klotho Proteins Male Membrane Proteins/genetics,metabolism Mice Mice, Transgenic Muscle, Skeletal/metabolism Oxidative Stress Paraquat/toxicity Protein Transport Proto-Oncogene Proteins c-akt/metabolism Somatomedins/metabolism Superoxide Dismutase
Chemicals
Forkhead Transcription Factors Insulin Membrane Proteins Somatomedins 8-Hydroxy-2'-Deoxyguanosine Superoxide Dismutase Proto-Oncogene Proteins c-akt Glucuronidase Klotho Proteins Deoxyguanosine Paraquat
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Yamamoto Masaya
Department of Pathology, the University of Texas Southwestern Medical Center, Dallas, 75390, USA.
Clark Jeremy D
Pastor Johanne V
Gurnani Prem
Nandi Animesh
Kurosu Hiroshi
Miyoshi Masayoshi
Ogawa Yasushi
Castrillon Diego H
Rosenblatt Kevin P
Kuro-o Makoto
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M509039200
Published
2005-11-11
Epub
2005-00-26
Pages
38029-34
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2515369
Subset
IM
Grants
NIA NIH HHS · R01 AG025326-03 · United States
NIA NIH HHS · R01 AG019712 · United States
NIA NIH HHS · R01AG19712 · United States
NIA NIH HHS · R01 AG019712-05 · United States
NIA NIH HHS · R01 AG025326 · United States
NIA NIH HHS · R01AG25326 · United States
External Links
PubMed source DOI: 10.1074/jbc.M509039200 PMC Full Text View journal details
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