Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy

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• 作者：Prachi Umbarkar^a ; Sarojini Singh^a ; ¹ ; Silpa Arkat^a ; ¹ ; S.L. Bodhankar^b ; Sathiyanarayanan Lohidasan^c ; Sandhya L. Sitasawad^a ; ^{ssitaswad@nccs.res.in" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MAO ; monoamine oxidase ; DCM ; diabetic cardiomyopathy ; I/R ; ischemia/reperfusion ; STZ ; streptozotocin ; CLG ; clorgyline ; HW ; heart weight ; BW ; body weight ; NE ; norepinephrine ; DHPG ; dihydroxyphenylglycol ; 5-HT ; 5-hydroxytryptamine ; ECG ; electrocardiography ; MABP ; mean arterial blood pressure ; LVSP ; left-ventricular systolic pressure ; LVEDP ; left-ventricular end-diastolic pressure ; ROS ; reactive oxygen species ; MDA ; malondialdehyde ; Prx ; peroxiredoxin ; UCP3 ; uncoupling protein 3 ; GPx ; glutathione p
• 刊名：Free Radical Biology and Medicine
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：87
• 期：Complete
• 页码：263-273
• 全文大小：4658 K

文摘

Oxidative stress is closely associated with the pathophysiology of diabetic cardiomyopathy (DCM). The mitochondrial flavoenzyme monoamine oxidase A (MAO-A) is an important source of oxidative stress in the myocardium. We sought to determine whether MAO-A plays a major role in modulating DCM. Diabetes was induced in Wistar rats by single intraperitoneal injection of streptozotocin (STZ). To investigate the role of MAO-A in the development of pathophysiological features of DCM, hyperglycemic and age-matched control rats were treated with or without the MAO-A-specific inhibitor clorgyline (CLG) at 1 mg/kg/day for 8 weeks. Diabetes upregulated MAO-A activity; elevated markers of oxidative stress such as cardiac lipid peroxidation, superoxide dismutase activity, and UCP3 protein expression; enhanced apoptotic cell death; and increased fibrosis. All these parameters were significantly attenuated by CLG treatment. In addition, treatment with CLG substantially prevented diabetes-induced cardiac contractile dysfunction as evidenced by decreased QRS, QT, and corrected QT intervals, measured by ECG, and LV systolic and LV end-diastolic pressure measured by microtip pressure transducer. These beneficial effects of CLG were seen despite the persistent hyperglycemic and hyperlipidemic environments in STZ-induced experimental diabetes. In summary, this study provides strong evidence that MAO-A is an important source of oxidative stress in the heart and that MAO-A-derived reactive oxygen species contribute to DCM.