Submitted on September 17, 2008
Revised on November 15, 2008
Accepted on December 7, 2008
Diabetes Impairs Exercise Training-associated Thioredoxin Response and Glutathione Status in Rat Brain
Zekine Lappalainen1, Jani Lappalainen2, Niku K.J. Oksala3, David E. Laaksonen4, Savita Khanna5, Chandan K. Sen5, and Mustafa Atalay1*
1 University of Kuopio, Institute of Biomedicine
2 Institute of Biomedicine, University of Kuopio
3 Tampere University Hospital
4 Kuopio University Hospital
5 Ohio State University Medical Center
* To whom correspondence should be addressed. E-mail: Mustafa.Atalay{at}uku.fi.
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 eight weeks 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 non-diabetic animals. Exercise training, however, increased TRX1 protein in non-diabetic 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.
