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SIRT3 Activation Inhibits Development of Diabetic Kidney Disease
Author(s) -
Myakala Komuraiah,
Wang Xiaoxin,
Lewien Pierce,
Wang Dong,
Luo Yuhuan,
HermanEdelstein Michal,
Rosenberg Avi Z.,
Levi Moshe
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.670.17
Subject(s) - sirt3 , diabetic nephropathy , sirtuin , medicine , sod2 , diabetes mellitus , pathogenesis , kidney , kidney disease , albuminuria , endocrinology , sirtuin 1 , renal function , chemistry , nad+ kinase , oxidative stress , downregulation and upregulation , biochemistry , gene , superoxide dismutase , enzyme
Diabetes continues to be the leading causes of kidney disease in the U.S. and around the world. Despite beneficial interventions implemented in patients with diabetes that mitigate some of its negative effects, kidney disease still progresses in most of these patients because the pathogenesis of diabetic kidney disease remains poorly understood. Recent evidence indicates that impairments in mitochondrial dynamics and function plays an important role in pathogenesis of diabetic kidney disease and brings promise to treatment strategies for improving mitochondrial function and the related pathways that may prevent or slow the progression of kidney disease. We aimed to test the influence of one key mitochondrial protein deacetylase, Sirtuin 3 (SIRT3) as a potential target for therapy in diabetic kidney disease. In kidney biopsies from human patients with diabetic nephropathy, there are decreases in SIRT3 mRNA and protein abundance in glomeruli and tubules. To test the effect of SIRT3 on the prevention of diabetic kidney disease, we conducted a study comparing three groups of mice: A control group, a diabetic group (db/db), and a diabetic group treated with nicotinamide riboside (NR), a precursor for NAD+, which is a co‐substrate required for SIRT3 activity. Treatment of diabetic mice with NR resulted in a) increase in renal SIRT3 activity as determined by significant decreases in total acetylated proteins and acetylated SOD2, significant decreases in b) albuminuria, c) mesangial expansion and glomerular area, d) accumulation of collagen IV protein, e) loss of synaptopodin and f) accumulation of 4‐HNE. In conclusion, SIRT3 plays an important role in diabetic kidney disease and increasing the SIRT3 activity may prevent the progression of diabetic kidney disease. Support or Funding Information NIH This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .