Age-associated cellular relocation of Sod 1 as a self-defense is a futile mechanism to prevent vascular aging.
Vascular aging is characterized by the presence of chronic oxidative stress. Although cytosolic Sod 1 has a key role in the detoxification of superoxide ((*)O(2)(-)), little is known about its importance in vascular aging. We found that inhibition of Sod 1 had no effect on (*)O2- generation. Furthermore, its expression decreased in an age-dependent manner. Interestingly, Sod 1 loses its membrane-association and is also lost from the caveolae with increasing age. Instead, a relocation of Sod 1 to the mitochondria takes place, presumably in an attempt to maintain mitochondrial integrity and to counter-balance age-associated oxidative stress. Unlike Sod 2, which is constitutively expressed in mitochondria to control (*)O2- radical fluxes, Sod 1 is not inactivated by peroxynitrite and is not nitrated as a function of age. These novel insights into oxidative stress-associated vascular aging and the understanding about how redox-systems are regulated in old age may identify new targets to ameliorate aging as the greatest cardiovascular risk factor.
van der Loo
Bernd
B
Clinic of Cardiology, Cardiovascular Centre, University Hospital Zurich, Switzerland. bernd.vanderloo@usz.ch
Bachschmid
Markus
M
Skepper
Jeremy N
JN
Labugger
Ralf
R
Schildknecht
Stefan
S
Hahn
Raphael
R
Müssig
Elisabeth
E
Gygi
Daniel
D
Lüscher
Thomas F
TF
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014018:Tissue Distribution
C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1