Diabetic changes in the redox status of the microsomal protein folding machinery.
Changes in assisted protein folding are largely unexplored in diabetes. In the present studies, we have identified a reductive shift in the redox status of rat liver microsomes after 4 weeks of streptozotocin-induced diabetes. This change was reflected by a significant increase in the total- and protein-sulfhydryl content, as well as in the free sulfhydryl groups of the major protein disulfide isomerases (PDIs), the 58 kDa PDI and the 57 kDa ERp57 but not other chaperones. A parallel decrease of the protein-disulfide oxidoreductase activity was detected in the microsomal fraction of diabetic livers. The oxidant of PDI, Ero1-Lalpha showed a more oxidized status in diabetic rats. Our results reveal major changes in the redox status of the endoplasmic reticulum and its redox chaperones in diabetic rats, which may contribute to the defective protein secretion of the diabetic liver.
Nardai
Gábor
G
Department of Medical Chemistry, Semmelweis University, P.O. Box 260, H-1444 Budapest 8, Hungary.
Stadler
Krisztián
K
Papp
Eszter
E
Korcsmáros
Tamás
T
Jakus
Judit
J
Csermely
Péter
P
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D003683:Dehydroascorbic Acid / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000096:biosynthesis; D017510:Protein Folding; D051381:Rats; D017208:Rats, Wistar
D005182:Flavin-Adenine Dinucleotide; D009247:NADH, NADPH Oxidoreductases; D019704:Protein Disulfide-Isomerases; D001205:Ascorbic Acid; D019803:Glutathione Disulfide; D003683:Dehydroascorbic Acid