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Catalase deficiency accelerates diabetic renal injury through peroxisomal dysfunction

Title
Catalase deficiency accelerates diabetic renal injury through peroxisomal dysfunction
Authors
Hwang I.Lee J.Huh J.Y.Park J.Lee H.B.Ho Y.-S.Ha H.
Ewha Authors
하헌주
SCOPUS Author ID
하헌주scopus
Issue Date
2012
Journal Title
Diabetes
ISSN
0012-1797JCR Link
Citation
vol. 61, no. 3, pp. 728 - 738
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Mitochondrial reactive oxygen species (ROS) play an important role in diabetes complications, including diabetic nephropathy (DN). Plasma free fatty acids (FFAs) as well as glucose are increased in diabetes, and peroxisomes and mitochondria participate in FFA oxidation in an interconnected fashion. Therefore, we investigated whether deficiency of catalase, a major peroxisomal antioxidant, accelerates DN through peroxisomal dysfunction and abnormal renal FFA metabolism. Diabetes was induced by multiple injections of low-dose streptozotocin into catalase knock-out (CKO) and wild-type (WT) C57BL/6 mice. Murine mesangial cells (MMCs) transfected with catalase small interfering RNA followed by catalase overexpression were used to further elucidate the role of endogenous catalase. Despite equivalent hyperglycemia, parameters of DN, along with markers of oxidative stress, were more accelerated in diabetic CKO mice than in diabetic WT mice up to 10 weeks of diabetes. CKO mice and MMCs showed impaired peroxisomal/mitochondrial biogenesis and FFA oxidation. Catalase deficiency increased mitochondrial ROS and fibronectin expression in response to FFAs, which were effectively restored by catalase overexpression or N-acetylcysteine. These data provide unprecedented evidence that FFA-induced peroxisomal dysfunction exacerbates DN and that endogenous catalase plays an important role in protecting the kidney from diabetic stress through maintaining peroxisomal and mitochondrial fitness. © 2012 by the American Diabetes Association.
DOI
10.2337/db11-0584
Appears in Collections:
약학대학 > 약학과 > Journal papers
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