Geldanamycin derivative ameliorates high fat diet-induced renal failure in diabetes

Hong Mei Zhang, Howard Dang, Amrita Kamat, Chih-ko Yeh, Bin Xian Zhang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Diabetic nephropathy is a serious complication of longstanding diabetes and its pathogenesis remains unclear. Oxidative stress may play a critical role in the pathogenesis and progression of diabetic nephropathy. Our previous studies have demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite generation in primary human kidney mesangial cells and heat shock protein 90β1 (hsp90β1) is indispensable for the PUFA action. Here we investigated the effects of high fat diet (HFD) on kidney function and structure of db/db mice, a widely used rodent model of type 2 diabetes. Our results indicated that HFD dramatically increased the 24 h-urine output and worsened albuminuria in db/db mice. Discontinuation of HFD reversed the exacerbated albuminuria but not the increased urine output. Prolonged HFD feeding resulted in early death of db/db mice, which was associated with oliguria and anuria. Treatment with the geldanamycin derivative, 17-(dimethylaminoehtylamino)-17-demethoxygeldanamycin (17-DMAG), an hsp90 inhibitor, preserved kidney function, and ameliorated glomerular and tubular damage by HFD. 17-DMAG also significantly extended survival of the animals and protected them from the high mortality associated with renal failure. The benefit effect of 17-DMAG on renal function and structure was associated with a decreased level of kidney nitrotyrosine and a diminished kidney mitochondrial Ca 2+ efflux in HFD-fed db/db mice. These results suggest that hsp90β1 is a potential target for the treatment of nephropathy and renal failure in diabetes.

Original languageEnglish (US)
Article numbere32746
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 6 2012

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High Fat Diet
renal failure
high fat diet
Nutrition
Medical problems
Renal Insufficiency
diabetes
Fats
Derivatives
Kidney
renal function
diabetic nephropathy
Albuminuria
mice
Diabetic Nephropathies
Heat-Shock Proteins
Unsaturated Fatty Acids
heat shock proteins
polyunsaturated fatty acids
urine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Geldanamycin derivative ameliorates high fat diet-induced renal failure in diabetes. / Zhang, Hong Mei; Dang, Howard; Kamat, Amrita; Yeh, Chih-ko; Zhang, Bin Xian.

In: PLoS One, Vol. 7, No. 3, e32746, 06.03.2012.

Research output: Contribution to journalArticle

Zhang, Hong Mei ; Dang, Howard ; Kamat, Amrita ; Yeh, Chih-ko ; Zhang, Bin Xian. / Geldanamycin derivative ameliorates high fat diet-induced renal failure in diabetes. In: PLoS One. 2012 ; Vol. 7, No. 3.
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