PMID- 28257842 OWN - NLM STAT- MEDLINE DCOM- 20170612 LR - 20191210 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 485 IP - 4 DP - 2017 Apr 15 TI - PICOT alleviates myocardial ischemia-reperfusion injury by reducing intracellular levels of reactive oxygen species. PG - 807-813 LID - S0006-291X(17)30436-9 [pii] LID - 10.1016/j.bbrc.2017.02.136 [doi] AB - Excessive generation of reactive oxygen species (ROS) is one of the main causes of myocardial ischemia-reperfusion (I/R) injury. In this study, we investigated the role of protein kinase C-interacting cousin of thioredoxin (PICOT; Grx3) during myocardial I/R using PICOT transgenic (TG) and knockdown (KD) mice. Infarction and apoptosis were attenuated in PICOT TG mice but exacerbated in PICOT KD mice upon I/R. In parallel, I/R-induced generation of ROS was attenuated in PICOT TG mice but exacerbated in PICOT KD mice. Angiotensin II (AngII)-mediated increases in ROS and free iron levels were also attenuated in cardiomyocytes isolated from PICOT TG mice but exacerbated in cardiomyocytes from PICOT KD mice. Accordingly, H(2)O(2)-mediated cell death was attenuated in cardiomyocytes isolated from PICOT TG mice but exacerbated in cardiomyocytes from PICOT KD mice. Taken together, these data show that PICOT alleviates myocardial I/R injury by regulating intracellular ROS and free iron levels. We suggest that PICOT presents a novel therapeutic strategy for myocardial I/R injury. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Kim, Jihwa AU - Kim J AD - College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-gu, Gwangju 61005, Republic of Korea. FAU - Kim, Jooyeon AU - Kim J AD - College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-gu, Gwangju 61005, Republic of Korea. FAU - Kook, Hyun AU - Kook H AD - Department of Pharmacology and Medical Research Center for Gene Regulation, Chonnam National University Medical School, 160 Baekseo-ro, Dong-ku, Gwangju 61469, Republic of Korea. FAU - Park, Woo Jin AU - Park WJ AD - College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-gu, Gwangju 61005, Republic of Korea. Electronic address: woojinpark@icloud.com. LA - eng PT - Journal Article DEP - 20170228 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Carrier Proteins) RN - 0 (Oxidants) RN - 0 (Reactive Oxygen Species) RN - 11128-99-7 (Angiotensin II) RN - BBX060AN9V (Hydrogen Peroxide) RN - E1UOL152H7 (Iron) RN - EC 1.8.4.2 (Protein Disulfide Reductase (Glutathione)) RN - EC 1.8.4.2 (Txnl2 protein, mouse) SB - IM MH - Angiotensin II/pharmacology MH - Animals MH - Carrier Proteins/genetics/*metabolism MH - Cell Survival/drug effects/genetics MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Hydrogen Peroxide/pharmacology MH - Intracellular Space/drug effects/*metabolism MH - Iron/metabolism MH - Male MH - Mice, Knockout MH - Mice, Transgenic MH - Microscopy, Fluorescence MH - Myocardial Reperfusion Injury/genetics/*metabolism MH - Myocytes, Cardiac/cytology/drug effects/*metabolism MH - Oxidants/pharmacology MH - Protein Disulfide Reductase (Glutathione) MH - Reactive Oxygen Species/*metabolism OTO - NOTNLM OT - Free iron OT - Glutaredoxin 3 OT - Heart OT - Ischemia-reperfusion injury OT - PICOT OT - ROS EDAT- 2017/03/05 06:00 MHDA- 2017/06/13 06:00 CRDT- 2017/03/05 06:00 PHST- 2017/02/22 00:00 [received] PHST- 2017/02/27 00:00 [accepted] PHST- 2017/03/05 06:00 [pubmed] PHST- 2017/06/13 06:00 [medline] PHST- 2017/03/05 06:00 [entrez] AID - S0006-291X(17)30436-9 [pii] AID - 10.1016/j.bbrc.2017.02.136 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2017 Apr 15;485(4):807-813. doi: 10.1016/j.bbrc.2017.02.136. Epub 2017 Feb 28.