<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bidwell, P. A.</style></author><author><style face="normal" font="default" size="100%">Liu, G. S.</style></author><author><style face="normal" font="default" size="100%">Nagarajan, N.</style></author><author><style face="normal" font="default" size="100%">Lam, C. K.</style></author><author><style face="normal" font="default" size="100%">Haghighi, K.</style></author><author><style face="normal" font="default" size="100%">Gardner, G.</style></author><author><style face="normal" font="default" size="100%">Cai, W. F.</style></author><author><style face="normal" font="default" size="100%">Zhao, W.</style></author><author><style face="normal" font="default" size="100%">Mugge, L.</style></author><author><style face="normal" font="default" size="100%">Vafiadaki, E.</style></author><author><style face="normal" font="default" size="100%">Sanoudou, D.</style></author><author><style face="normal" font="default" size="100%">Rubinstein, J.</style></author><author><style face="normal" font="default" size="100%">Lebeche, D.</style></author><author><style face="normal" font="default" size="100%">Hajjar, R.</style></author><author><style face="normal" font="default" size="100%">Sadoshima, J.</style></author><author><style face="normal" font="default" size="100%">Kranias, EG</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">HAX-1 regulates SERCA2a oxidation and degradation</style></title><secondary-title><style face="normal" font="default" size="100%">J Mol Cell CardiolJ Mol Cell CardiolJ Mol Cell Cardiol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Journal of molecular and cellular cardiology</style></alt-title><short-title><style face="normal" font="default" size="100%">Journal of molecular and cellular cardiologyJournal of molecular and cellular cardiology</style></short-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">*Proteolysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Adaptor Proteins, Signal Transducing/genetics/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Calpain/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Endoplasmic Reticulum/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Deletion</style></keyword><keyword><style  face="normal" font="default" size="100%">Heart Failure/genetics/pathology/physiopathology</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Intracellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Myocardial Contraction</style></keyword><keyword><style  face="normal" font="default" size="100%">Myocardial Reperfusion Injury/pathology/physiopathology</style></keyword><keyword><style  face="normal" font="default" size="100%">Myocardium/pathology</style></keyword><keyword><style  face="normal" font="default" size="100%">Myocytes, Cardiac/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">NADPH Oxidase 4/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxidation-Reduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxidative Stress</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteins/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Rats, Wistar</style></keyword><keyword><style  face="normal" font="default" size="100%">Reactive Oxygen Species/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Recovery of Function</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Messenger/genetics/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Sarcoplasmic Reticulum Calcium-Transporting ATPases/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Sarcoplasmic Reticulum/metabolism</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jan</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">114</style></volume><pages><style face="normal" font="default" size="100%">220-233</style></pages><isbn><style face="normal" font="default" size="100%">1095-8584 (Electronic)0022-2828 (Linking)</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Ischemia/reperfusion injury is associated with contractile dysfunction and increased cardiomyocyte death. Overexpression of the hematopoietic lineage substrate-1-associated protein X-1 (HAX-1) has been shown to protect from cellular injury but the function of endogenous HAX-1 remains obscure due to early lethality of the knockout mouse. Herein we generated a cardiac-specific and inducible HAX-1 deficient model, which uncovered an unexpected role of HAX-1 in regulation of sarco/endoplasmic reticulum Ca-ATPase (SERCA2a) in ischemia/reperfusion injury. Although ablation of HAX-1 in the adult heart elicited no morphological alterations under non-stress conditions, it diminished contractile recovery and increased infarct size upon ischemia/reperfusion injury. These detrimental effects were associated with increased loss of SERCA2a. Enhanced SERCA2a degradation was not due to alterations in calpain and calpastatin levels or calpain activity. Conversely, HAX-1 overexpression improved contractile recovery and maintained SERCA2a levels. The regulatory effects of HAX-1 on SERCA2a degradation were observed at multiple levels, including intact hearts, isolated cardiomyocytes and sarcoplasmic reticulum microsomes. Mechanistically, HAX-1 ablation elicited increased production of reactive oxygen species at the sarco/endoplasic reticulum compartment, resulting in SERCA2a oxidation and a predisposition to its proteolysis. This effect may be mediated by NAPDH oxidase 4 (NOX4), a novel binding partner of HAX-1. Accordingly, NOX inhibition with apocynin abrogated the effects of HAX-1 ablation in hearts subjected to ischemia/reperfusion injury. Taken together, our findings reveal a role of HAX-1 in the regulation of oxidative stress and SERCA2a degradation, implicating its importance in calcium homeostasis and cell survival pathways.</style></abstract><accession-num><style face="normal" font="default" size="100%">29169992</style></accession-num><notes><style face="normal" font="default" size="100%">Bidwell, Philip ALiu, Guan-ShengNagarajan, NarayaniLam, Chi KeungHaghighi, KobraGardner, GeorgeCai, Wen-FengZhao, WenMugge, LukeVafiadaki, ElizabethSanoudou, DespinaRubinstein, JackLebeche, DjamelHajjar, RogerSadoshima, JunichiKranias, Evangelia GengR01 HL026057/HL/NHLBI NIH HHS/R01 HL064018/HL/NHLBI NIH HHS/R01 HL129814/HL/NHLBI NIH HHS/T32 HL125204/HL/NHLBI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tEngland2017/11/25 06:00J Mol Cell Cardiol. 2018 Jan;114:220-233. doi: 10.1016/j.yjmcc.2017.11.014. Epub 2017 Nov 21.</style></notes><custom2><style face="normal" font="default" size="100%">5801168</style></custom2><auth-address><style face="normal" font="default" size="100%">Department of Pharmacology and Systems Physiology, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece.Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece; 4th Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.Division of Cardiology, Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.Cardiovascular Research Center, Ichan School of Medicine at Mount Sinai, New York, NY, USA.Department of Pharmacology and Systems Physiology, University of Cincinnati, College of Medicine, Cincinnati, OH, USA; Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece. Electronic address: Litsa.Kranias@uc.edu.</style></auth-address></record></records></xml>