title: PICOT alleviates myocardial ischemia-reperfusion injury by reducing intracellular levels of reactive oxygen species.
abstract: 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, H2O2-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.
authors.affiliation: 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.
authors.forename: Jihwa
authors.initials: J
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Jooyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
authors.affiliation: 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.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D011490:Protein Disulfide Reductase (Glutathione); D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D007501:Iron; D011490:Protein Disulfide Reductase (Glutathione); C498606:Txnl2 protein, mouse
keywords: Free iron; Glutaredoxin 3; Heart; Ischemia-reperfusion injury; PICOT; ROS