Reduced expression of lipoic acid synthase accelerates diabetic nephropathy.
Authors Yi X, Xu L, Hiller S, Kim HS, Nickeleit V, James LR, Maeda N
Submitted By Nobuyo Maeda on 2/22/2012
Status Published
Journal Journal of the American Society of Nephrology : JASN
Year 2012
Date Published 1/1/2012
Volume : Pages 23 : 103 - 111
PubMed Reference 22021711
Abstract Oxidative stress contributes to the pathogenesis of diabetic nephropathy. In
mitochondria, lipoic acid synthase produces a-lipoic acid, an antioxidant and an
essential cofactor in a-ketoacid dehydrogenase complexes, which participate in
glucose oxidation and ATP generation. Administration of lipoic acid abrogates
diabetic nephropathy in animal models, but whether lower production of
endogenous lipoic acid promotes diabetic nephropathy is unknown. Here, we
crossed mice heterozygous for lipoic acid synthase deficiency (Lias(+/-)) with
Ins2(Akita/+) mice, a well characterized model of type 1 diabetes. Double mutant
mice had more overt diabetic nephropathy, including microalbuminuria, glomerular
basement thickening, mesangial matrix expansion, and hypertension, compared with
Lias(+/+)Ins2(Akita/+) controls. We also identified proximal tubules as a major
site for generation of superoxide anions during diabetic nephropathy.
Mitochondria in proximal tubular cells were particularly sensitive to damage in
diabetic mice with reduced lipoic acid production. These results suggest that
lipoic acid synthase deficiency increases oxidative stress and accelerates the
development of diabetic nephropathy.

Investigators with authorship
Nobuyo MaedaUniversity of North Carolina