PMID- 27393003 OWN - NLM STAT- MEDLINE DCOM- 20180104 LR - 20180122 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 97 DP - 2016 Aug TI - Mitochondrial Peroxiredoxin-3 protects against hyperglycemia induced myocardial damage in Diabetic cardiomyopathy. PG - 489-500 LID - S0891-5849(16)30307-0 [pii] LID - 10.1016/j.freeradbiomed.2016.06.019 [doi] AB - Mitochondrial oxidative stress has emerged as a key contributor towards the development of diabetic cardiomyopathy. Peroxiredoxin-3 (Prx-3), a mitochondrial antioxidant, scavenges H2O2 and offers protection against ROS related pathologies. We observed a decrease in the expression of Prx-3 in the hearts of streptozotocin (STZ) induced diabetic rats, and also high glucose treated H9c2 cardiac cells, which may augment oxidative stress mediated damage. Hence we hypothesized that overexpression of Prx-3 could prevent the cardiac damage associated with diabetes. In this study we used quercetin (QUE) to achieve Prx-3 induction in vivo, while a Prx-3 overexpressing H9c2 cell line was employed for carrying out in vitro studies. Diabetes was induced in Wistar rats by a single intraperitoneal injection of STZ. Quercetin (50mg/kg body weight) was delivered orally to hyperglycemic and age matched control rats for 2 months. Quercetin treatment induced the myocardial expression of Prx-3 but not Prx-5 both in control and STZ rats. Prx-3 induction by quercetin prevented diabetes induced oxidative stress as confirmed by decrease in expression of markers such as 4-HNE and mitochondrial uncoupling protein, UCP-3. It was also successful in reducing cardiac cell apoptosis, hypertrophy and fibrosis leading to amelioration of cardiac contractility defects. Overexpression of Prx-3 in cultured H9c2 cardiac cells could significantly diminish high glucose inflicted mitochondrial oxidative damage and apoptosis, thus strengthening our hypothesis. These results suggest that diabetes induced cardiomyopathy can be prevented by elevating Prx-3 levels thereby providing extensive protection to the diabetic heart. CI - Copyright (c) 2016. Published by Elsevier Inc. FAU - Arkat, Silpa AU - Arkat S AD - National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India. Electronic address: silpa.knlarkat@gmail.com. FAU - Umbarkar, Prachi AU - Umbarkar P AD - National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India. Electronic address: prachiu37@gmail.com. FAU - Singh, Sarojini AU - Singh S AD - National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India. Electronic address: sarojinisingh10@gmail.com. FAU - Sitasawad, Sandhya L AU - Sitasawad SL AD - National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India. Electronic address: ssitaswad@nccs.res.in. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160705 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (Antioxidants) RN - 0 (Blood Glucose) RN - 0 (Reactive Oxygen Species) RN - 9IKM0I5T1E (Quercetin) RN - EC 1.11.1.15 (Peroxiredoxin III) RN - EC 1.8.1.9 (Thioredoxin Reductase 2) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Blood Glucose MH - Cell Line MH - Diabetes Mellitus, Experimental/blood/*enzymology MH - Diabetic Cardiomyopathies/blood/*enzymology MH - Enzyme Repression MH - Gene Expression MH - Hyperglycemia/blood/*enzymology MH - Male MH - Oxidative Stress MH - Peroxiredoxin III/*physiology MH - Protective Factors MH - Quercetin/pharmacology MH - Rats, Wistar MH - Reactive Oxygen Species/metabolism MH - Thioredoxin Reductase 2/metabolism OTO - NOTNLM OT - Apoptosis OT - Cardiac dysfunction OT - Diabetic cardiomyopathy OT - Oxidative stress OT - Peroxiredoxin-3 EDAT- 2016/07/10 06:00 MHDA- 2018/01/05 06:00 CRDT- 2016/07/10 06:00 PHST- 2016/01/18 00:00 [received] PHST- 2016/06/15 00:00 [revised] PHST- 2016/06/18 00:00 [accepted] PHST- 2016/07/10 06:00 [entrez] PHST- 2016/07/10 06:00 [pubmed] PHST- 2018/01/05 06:00 [medline] AID - S0891-5849(16)30307-0 [pii] AID - 10.1016/j.freeradbiomed.2016.06.019 [doi] PST - ppublish SO - Free Radic Biol Med. 2016 Aug;97:489-500. doi: 10.1016/j.freeradbiomed.2016.06.019. Epub 2016 Jul 5.