Diabetes impairs exercise training-associated thioredoxin response and glutathione status in rat brain.
Regular exercise plays an important preventive and therapeutic role in oxidative stress-associated diseases such as diabetes and its complications. Thiol antioxidants including thioredoxin (TRX) and glutathione (GSH) have a crucial role in controlling cellular redox status. In this study, the effects of 8 wk of exercise training on brain TRX and GSH systems, and antioxidant enzymes were tested in rats with or without streptozotocin-induced diabetes. We found that in untrained animals, the levels of TRX-1 (TRX1) protein and activity, and thioredoxin-interacting protein (TXNip) were similar in diabetic and nondiabetic animals. Exercise training, however, increased TRX1 protein in nondiabetic animals without affecting TXNip levels, whereas diabetes inhibited the effect of training on TRX1 protein and also increased TXNip mRNA. In addition, the proportion of oxidized glutathione (GSSG) to total GSH was increased in animals with diabetes, indicating altered redox status and possibly increased oxidative stress. Glutathione peroxidase-1 (GPX1) levels were not affected by diabetes or exercise training, although diabetes increased total GPX activity. Both diabetes and exercise training decreased glutathione reductase (GRD) activity and cytosolic superoxide dismutase (Cu,Zn-SOD) levels. Nevertheless, diabetes or training had no effect on Cu,Zn-SOD mRNA, Mn-SOD protein, total SOD activity, or catalase mRNA, protein, or activity. Our findings suggest that exercise training increases TRX1 levels in brain without a concomitant rise in TXNip, and that experimental diabetes is associated with an incomplete TRX response to training. Increased oxidative stress may be both a cause and a consequence of perturbed antioxidant defenses in the diabetic brain.
Lappalainen
Zekine
Z
Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
Lappalainen
Jani
J
Oksala
Niku K J
NK
Laaksonen
David E
DE
Khanna
Savita
S
Sen
Chandan K
CK
Atalay
Mustafa
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D005082:Physical Exertion; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D000975:Antioxidants; D001786:Blood Glucose; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C493796:TXNIP protein, rat; C495697:Txn1 protein, rat; D013879:Thioredoxins; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D019803:Glutathione Disulfide