دورية أكاديمية
Resveratrol ameliorates cardiac oxidative stress in diabetes through deacetylation of NFkB-p65 and histone 3.
العنوان: | Resveratrol ameliorates cardiac oxidative stress in diabetes through deacetylation of NFkB-p65 and histone 3. |
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المؤلفون: | Bagul PK; Division of Medicinal Chemistry Pharmacology, Indian Institute of Chemical Technology (IICT), Hyderabad, 500607, India; Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, 121001, India., Deepthi N; Division of Medicinal Chemistry Pharmacology, Indian Institute of Chemical Technology (IICT), Hyderabad, 500607, India., Sultana R; Division of Medicinal Chemistry Pharmacology, Indian Institute of Chemical Technology (IICT), Hyderabad, 500607, India., Banerjee SK; Division of Medicinal Chemistry Pharmacology, Indian Institute of Chemical Technology (IICT), Hyderabad, 500607, India; Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, 121001, India. Electronic address: skbanerjee@thsti.res.in. |
المصدر: | The Journal of nutritional biochemistry [J Nutr Biochem] 2015 Nov; Vol. 26 (11), pp. 1298-307. Date of Electronic Publication: 2015 Jul 23. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 9010081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4847 (Electronic) Linking ISSN: 09552863 NLM ISO Abbreviation: J Nutr Biochem Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <1996->: New York, NY : Elsevier Science Original Publication: Stoneham, MA, USA : Butterworths, c1990- |
مواضيع طبية MeSH: | Diabetes Mellitus, Experimental/*drug therapy , Histones/*metabolism , Oxidative Stress/*drug effects , Stilbenes/*pharmacology , Transcription Factor RelA/*metabolism, Acetylation/drug effects ; Animals ; Cardiomegaly/drug therapy ; Cardiomegaly/physiopathology ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/physiopathology ; Fructosamine/metabolism ; Heart/drug effects ; Heart/physiopathology ; Male ; NADPH Oxidases/metabolism ; Nitric Oxide/metabolism ; Rats, Sprague-Dawley ; Resveratrol ; Sirtuin 1 ; Superoxide Dismutase/metabolism |
مستخلص: | Resveratrol, a phytoalexin, has recently gained attention for protective effects against metabolic and cardiac diseases. The beneficial effects of resveratrol have been linked to sirtuin-1 (SIRT-1) activation. However, little is known about the effect of resveratrol in cardiac complications associated with diabetes. Here, we have demonstrated that resveratrol ameliorates cardiac hypertrophy, electrocardiographic abnormalities and oxidative stress in the fructose-fed diabetic rat heart. Mechanistic studies revealed that fructose feeding to Sprague-Dawley rats over a period of 8 weeks leads to cardiac hypertrophy and increased oxidative stress through increased activity of NADPH oxidase (NOX) and reactive oxygen species production. We found increased activity of nuclear factor kappa B (NFkB) p-65 along with decreased SIRT-1 activity in the diabetic heart. Resveratrol activates SIRT-1, which deacetylates NFkB-p65 at lysine 310 and histone 3 (H3) at lysine 9 position. SIRT1 activation leads to decreased binding of NFkB-p65 to DNA and attenuated cardiac hypertrophy and oxidative stress through reduced transcription of NADPH oxidase subunits. In vitro analysis also revealed that SIRT-1 activation by resveratrol is associated with decreased NFkB-p65 activity and NOX transcription. Similarly, knockdown or inhibition of SIRT1 in H9C2 cells increased acetylation of NFkB-p65 K310 and H3K9. Overall, our data demonstrated that SIRT-1 activation by resveratrol leads to deacetylation of both NFkB-p65 and H3, thereby attenuating cardiac oxidative stress and complications in diabetes. (Copyright © 2015 Elsevier Inc. All rights reserved.) |
فهرسة مساهمة: | Keywords: Acetylation; Diabetic cardiomyopathy; Histone; NFkB; Oxidative stress; Resveratrol; SIRT-1 |
المشرفين على المادة: | 0 (Histones) 0 (Rela protein, rat) 0 (Stilbenes) 0 (Transcription Factor RelA) 31C4KY9ESH (Nitric Oxide) 4429-04-3 (Fructosamine) EC 1.15.1.1 (Superoxide Dismutase) EC 1.6.3.- (NADPH Oxidases) EC 3.5.1.- (Sirt1 protein, rat) EC 3.5.1.- (Sirtuin 1) Q369O8926L (Resveratrol) |
تواريخ الأحداث: | Date Created: 20150824 Date Completed: 20170925 Latest Revision: 20181202 |
رمز التحديث: | 20240628 |
DOI: | 10.1016/j.jnutbio.2015.06.006 |
PMID: | 26298192 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1873-4847 |
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DOI: | 10.1016/j.jnutbio.2015.06.006 |