Proteomics profiling of hepatic mitochondria in heterozygous Sod2+/- mice, an animal model of discreet mitochondrial oxidative stress.
The heterozygous superoxide dismutase 2 (SOD2) gene knockout (Sod2+/-) mouse model has been increasingly used in cardiovascular and age research, neurobiology, and pharmacology/toxicology. These mutant mice exhibit mild oxidant stress in mitochondria but remain clinically inconspicuous. Although the Sod2+/- mouse has been characterized with respect to mitochondrial function and transcript expression of certain individual genes, the effects of the singular loss of the Sod2 allele on the global expression of hepatic mitochondrial proteins remains unknown. We therefore performed a differential analysis of the hepatic mitochondrial proteome from Sod2+/- mice and wild-type mice in order to identify the consequences of partial Sod2 deletion. Using 2-D difference gel electrophoresis (DIGE) coupled with MALDI-MS/MS, we found approximately 1500 protein spots, of which 57 were differentially expressed (> or =1.5-fold change). Both SOD 1 and 2 were downregulated, but other antioxidant enzymes and related proteins were upregulated (<two-fold). The data indicate that heterozygous Sod2+/- mice exhibit a mild mitochondrial oxidative stress which is partly compensated by the antioxidant defense system linked to the tricarboxylic acid (TCA) cycle, urea cycle, beta-oxidation, and oxidative phosphorylation (OXPHOS). The results of this study are compatible with our hypothesis that the Sod2+/- mouse is a suitable animal model for studying clinically silent mitochondrial abnormalities.
Lee
Yie Hou
YH
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Boelsterli
Urs A
UA
Lin
Qingsong
Q
Chung
Maxey C M
MC
D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D020543:Proteome / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D053719:Tandem Mass Spectrometry / Q000379:methods; D000099156:Superoxide Dismutase 2
D020543:Proteome; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2