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Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy.
Free Radic Biol Med 2015; 87:263-73FR

Abstract

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.

Authors+Show Affiliations

National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India.National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India.National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India.Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, India.Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, India.National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India. Electronic address: ssitaswad@nccs.res.in.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26122707

Citation

Umbarkar, Prachi, et al. "Monoamine oxidase-A Is an Important Source of Oxidative Stress and Promotes Cardiac Dysfunction, Apoptosis, and Fibrosis in Diabetic Cardiomyopathy." Free Radical Biology & Medicine, vol. 87, 2015, pp. 263-73.
Umbarkar P, Singh S, Arkat S, et al. Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy. Free Radic Biol Med. 2015;87:263-73.
Umbarkar, P., Singh, S., Arkat, S., Bodhankar, S. L., Lohidasan, S., & Sitasawad, S. L. (2015). Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy. Free Radical Biology & Medicine, 87, pp. 263-73. doi:10.1016/j.freeradbiomed.2015.06.025.
Umbarkar P, et al. Monoamine oxidase-A Is an Important Source of Oxidative Stress and Promotes Cardiac Dysfunction, Apoptosis, and Fibrosis in Diabetic Cardiomyopathy. Free Radic Biol Med. 2015;87:263-73. PubMed PMID: 26122707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy. AU - Umbarkar,Prachi, AU - Singh,Sarojini, AU - Arkat,Silpa, AU - Bodhankar,S L, AU - Lohidasan,Sathiyanarayanan, AU - Sitasawad,Sandhya L, Y1 - 2015/06/26/ PY - 2015/02/06/received PY - 2015/05/22/revised PY - 2015/06/09/accepted PY - 2015/7/1/entrez PY - 2015/7/1/pubmed PY - 2016/8/2/medline KW - Apoptosis KW - Cardiac dysfunction KW - Diabetic cardiomyopathy KW - Free radicals KW - Monoamine oxidase A KW - Oxidative stress SP - 263 EP - 73 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 87 N2 - 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. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/26122707/Monoamine_oxidase_A_is_an_important_source_of_oxidative_stress_and_promotes_cardiac_dysfunction_apoptosis_and_fibrosis_in_diabetic_cardiomyopathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(15)00293-2 DB - PRIME DP - Unbound Medicine ER -