| RRC ID |
12205
|
| Author |
Nishio Y, Kashiwagi A, Taki H, Shinozaki K, Maeno Y, Kojima H, Maegawa H, Haneda M, Hidaka H, Yasuda H, Horiike K, Kikkawa R.
|
| Title |
Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.
|
| Journal |
Diabetes
|
| Abstract |
Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P < 0.01 and P < 0.05, respectively). Insulin treatment also consistently prevented changes in the mRNA content of heme oxygenase-1. The oral administration of an antioxidant, probucol, to these diabetic rats partially prevented the elevation of the activity of both NF-kappaB and AP-1, and normalized the mRNA content of heme oxygenase-1 without producing any change in the plasma glucose concentration. These results suggest that elevated oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.
|
| Volume |
47(8)
|
| Pages |
1318-25
|
| Published |
1998-8-1
|
| DOI |
10.2337/diab.47.8.1318
|
| PMID |
9703334
|
| MeSH |
Animals
Antioxidants / pharmacology
Diabetes Mellitus, Experimental / genetics*
Diabetes Mellitus, Experimental / metabolism*
Gene Expression* / physiology
Heart / physiopathology*
Heme Oxygenase (Decyclizing) / genetics
Heme Oxygenase-1
Lipid Peroxides / metabolism
Male
Myocardium / metabolism*
Oxidoreductases / genetics
Probucol / pharmacology
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Transcription Factors / genetics*
Transcription Factors / physiology*
|
| IF |
7.72
|
| Times Cited |
68
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
|
| Resource |
| DNA material |
pRHO1 Rat heme oxygenase cDNA (RDB01208) |
