Reduced expression of lipoic acid synthase accelerates diabetic nephropathy

Xianwen Yi, Longquan Xu, Sylvia Hiller, Hyung Suk Kim, Volker Nickeleit, Leighton R James, Nobuyo Maeda

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 hadmore overt diabetic nephropathy, includingmicroalbuminuria, 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 diabeticmice with reduced lipoic acid production. These results suggest that lipoic acid synthase deficiency increases oxidative stress and accelerates the development of diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)103-111
Number of pages9
JournalJournal of the American Society of Nephrology
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Diabetic Nephropathies
Thioctic Acid
Mitochondria
Oxidative Stress
Type 1 Diabetes Mellitus
Superoxides
lipoic acid synthase
Oxidoreductases
Animal Models
Antioxidants
Adenosine Triphosphate
Hypertension
Glucose

ASJC Scopus subject areas

  • Nephrology

Cite this

Reduced expression of lipoic acid synthase accelerates diabetic nephropathy. / Yi, Xianwen; Xu, Longquan; Hiller, Sylvia; Kim, Hyung Suk; Nickeleit, Volker; James, Leighton R; Maeda, Nobuyo.

In: Journal of the American Society of Nephrology, Vol. 23, No. 1, 01.01.2012, p. 103-111.

Research output: Contribution to journalArticle

Yi, Xianwen ; Xu, Longquan ; Hiller, Sylvia ; Kim, Hyung Suk ; Nickeleit, Volker ; James, Leighton R ; Maeda, Nobuyo. / Reduced expression of lipoic acid synthase accelerates diabetic nephropathy. In: Journal of the American Society of Nephrology. 2012 ; Vol. 23, No. 1. pp. 103-111.
@article{a75c99c7fc7d4baf94cd4b24e4b043ce,
title = "Reduced expression of lipoic acid synthase accelerates diabetic nephropathy",
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 hadmore overt diabetic nephropathy, includingmicroalbuminuria, 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 diabeticmice with reduced lipoic acid production. These results suggest that lipoic acid synthase deficiency increases oxidative stress and accelerates the development of diabetic nephropathy.",
author = "Xianwen Yi and Longquan Xu and Sylvia Hiller and Kim, {Hyung Suk} and Volker Nickeleit and James, {Leighton R} and Nobuyo Maeda",
year = "2012",
month = "1",
day = "1",
doi = "10.1681/ASN.2011010003",
language = "English (US)",
volume = "23",
pages = "103--111",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "1",

}

TY - JOUR

T1 - Reduced expression of lipoic acid synthase accelerates diabetic nephropathy

AU - Yi, Xianwen

AU - Xu, Longquan

AU - Hiller, Sylvia

AU - Kim, Hyung Suk

AU - Nickeleit, Volker

AU - James, Leighton R

AU - Maeda, Nobuyo

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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 hadmore overt diabetic nephropathy, includingmicroalbuminuria, 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 diabeticmice with reduced lipoic acid production. These results suggest that lipoic acid synthase deficiency increases oxidative stress and accelerates the development of diabetic nephropathy.

AB - 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 hadmore overt diabetic nephropathy, includingmicroalbuminuria, 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 diabeticmice with reduced lipoic acid production. These results suggest that lipoic acid synthase deficiency increases oxidative stress and accelerates the development of diabetic nephropathy.

UR - http://www.scopus.com/inward/record.url?scp=84862937339&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862937339&partnerID=8YFLogxK

U2 - 10.1681/ASN.2011010003

DO - 10.1681/ASN.2011010003

M3 - Article

C2 - 22021711

AN - SCOPUS:84862937339

VL - 23

SP - 103

EP - 111

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 1

ER -