Quantitative protein profiling in heart mitochondria from diabetic rats.
Quantitative protein profiling based on in vitro stable isotope labeling, two-dimensional polyacrylamide gel electrophoresis, and mass spectrometry is an accurate and reliable approach to measure simultaneously the relative abundance of many individual proteins within two different samples. In the present study, it was used to define a set of alterations caused by diabetes in heart mitochondria from streptozotocin-treated rats. We demonstrated that the expression of proteins from the myocardial tricarboxylic acid cycle was not altered in diabetes. However, up-regulation of the fatty acid beta-oxidation favored fatty acids over glucose as a source of acetyl CoA for the tricarboxylic acid cycle. Protein levels for several proteins involved in electron transport were modestly decreased. Whether this may depress overall ATP production remains to be established, since the protein level of ATP synthase seems to be unchanged. Other changes include down-regulation of protein levels for creatine kinase, voltage-dependent anion channel 1 (VDAC-1), HSP60, and Grp75. The mitochondria-associated level of albumin was decreased, while the level of catalase was substantially increased. All of the changes were evident as early as 1 week after streptozotocin administration. Taken together, these data point to a rapid and highly coordinated regulation of mitochondrial protein expression that occurs during the heart adaptation to diabetes.
Turko
Illarion V
IV
Department of Integrative Biology and Pharmacology and Institute of Molecular Medicine, University of Texas Medical School, Houston, Texas 77030, USA.
Murad
Ferid
F
D000595:Amino Acid Sequence; D000818:Animals; D002952:Citric Acid Cycle / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics*; D004798:Enzymes / Q000235:genetics*; D005786:Gene Expression Regulation; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D008969:Molecular Sequence Data; D010085:Oxidative Phosphorylation; D010446:Peptide Fragments / Q000737:chemistry; D040081:Protein Array Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004798:Enzymes; D010446:Peptide Fragments