Alpha-lipoic acid upregulates antioxidant enzyme gene expression and enzymatic activity in diabetic rat kidneys through an O-GlcNAc-dependent mechanism.
Purpose: The combined hyperglycemia lowering and antioxidant actions of α-lipoic acid (LA) contribute to its usefulness in preventing renal injury and other diabetic complications. The precise mechanisms by which LA alters diabetic oxidative renal injury are not known. We hypothesized that LA throug...
| Publicado en: | European Journal of Nutrition Vol. 52; no. 5; pp. 1461 - 1474 |
|---|---|
| Autores principales: | , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Aug2013
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104082629&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104082629 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14366207 CR0 jtl: European Journal of Nutrition issn: 14366207 maglogo: N pubinfo: dt: Aug2013 vid: 52 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104082629 89151484 10.1007/s00394-012-0452-z NLM23064900 104082629 ppf: 1461 ppct: 13 formats: fmt: @attributes: type: P tig: atl: Alpha-lipoic acid upregulates antioxidant enzyme gene expression and enzymatic activity in diabetic rat kidneys through an O-GlcNAc-dependent mechanism. aug: au: Arambašić, Jelena Mihailović, Mirjana Uskoković, Aleksandra Dinić, Svetlana Grdović, Nevena Marković, Jelena Poznanović, Goran Bajec, Djordje Vidaković, Melita affil: Department of Molecular Biology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142 10060 Belgrade Serbia sug: subj: Gene Expression Glucosamine Metabolism Antioxidants Metabolism Diabetes Mellitus Metabolism Kidney Drug Effects Fatty Acids Pharmacodynamics Blood Glucose Metabolism DNA Drug Effects Diabetes Mellitus Chemically Induced Glutathione Metabolism Lipid Peroxidation Drug Effects Oxidative Stress Drug Effects Kidney Diseases Prevention and Control Hyperglycemia Drug Therapy Signal Transduction Superoxide Dismutase Metabolism Animal Studies Descriptive Statistics Analysis of Variance Funding Source ab: Purpose: The combined hyperglycemia lowering and antioxidant actions of α-lipoic acid (LA) contribute to its usefulness in preventing renal injury and other diabetic complications. The precise mechanisms by which LA alters diabetic oxidative renal injury are not known. We hypothesized that LA through its hypoglycemic effect lowers O-GlcNAcylation which influences the expression and activities of antioxidant enzymes which assume important roles in preventing diabetes-induced oxidative renal injury. Methods: An experimental model of diabetes was induced in rats by the administration of 40 mg/kg streptozotocin (STZ) intraperitoneally (i.p.) for five consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration. Results: An improved glycemic status of LA-treated diabetic rats was accompanied by a significant suppression of oxidative stress and a reduction of oxidative damage of lipids, proteins and DNA. LA treatment normalized CuZn-superoxide dismutase (SOD) and catalase activities in renal tissue of diabetic rats. These changes were allied with upregulated gene expression and lower levels of O-GlcNA glycosylation. The accompanying increase in MnSOD activity was only linked with upregulated gene expression. The observed antioxidant enzyme gene regulation was accompanied by nuclear translocation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), enhanced expression of heat shock proteins (HSPs) and by reduction in O-GlcNAcylation of HSP90, HSP70, and extracellular regulated kinase and p38. Conclusion: α-Lipoic acid administration activates a coordinated cytoprotective response against diabetes-induced oxidative injury in kidney tissue through an O-GlcNAc-dependent mechanism. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|