title: Cardiac-specific overexpression of catalase rescues ventricular myocytes from ethanol-induced cardiac contractile defect.
abstract: Oxidative stress is intimately involved in alcoholic cardiomyopathy. Catalase is responsible for detoxification of hydrogen peroxide (H(2)O(2)) and may interfere with ethanol-induced cardiac toxicity. To test this hypothesis, a transgenic mouse line was produced to overexpress catalase (~50-fold) in the heart, ranging from sarcoplasm, the nucleus and peroxisomes within myocytes. Mechanical and intracellular Ca(2+) properties were evaluated in ventricular myocytes from catalase transgenic (CAT) and wild-type FVB mice. Protein abundance of sarco (endo) plasmic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), Na(+)/Ca(2+) exchanger (NCX), dihydropyridine Ca(2+) receptor (DHPR), ryanodine receptor (RyR), Akt and phosphorylated Akt (pAkt) were measured by western blot. CAT itself did not alter body and organ weights, as well as myocyte contractile properties. Acute exposure of ethanol elicited a concentration-dependent depression in cell shortening and intracellular Ca(2+) in FVB mice with maximal inhibitions of 65.4% and 35.8%, respectively. The ethanol-induced cardiac depression was significantly attenuated in myocytes from CAT with maximal inhibitions of 42.4% and 27.3%. CAT also abrogated the ethanol-induced inhibition of maximal velocity of shortening/relengthening, prolongation of relengthening duration and intracellular Ca(2+) clearing time. Cell shortening at different extracellular Ca(2+) revealed stronger myocyte-shortening amplitude under lower (0.5 mM) Ca(2+) in CAT mice. Protein expression of NCX, RyR, Akt and pAkt were elevated in myocytes from CAT mice, while those of SERCA, PLB and DHPR were not affected. In conclusion, our data suggest that catalase overexpression may protect cardiac myocytes from ethanol-induced contractile defect, partially through improved intracellular Ca(2+) handling and Akt signaling.
authors.affiliation: Division of Pharmaceutical Sciences, University of Wyoming College of Health Sciences, WY 82071-3375, Laramie, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Klein
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Alberle
authors.forename: Faye L
authors.initials: FL
authors.lastname: Norby
authors.forename: Bonnie H
authors.initials: BH
authors.lastname: Ren
authors.forename: Jinhong
authors.initials: J
authors.lastname: Duan
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis; D002374:Catalase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress; D020675:Peroxisomes / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis; D013050:Spectrometry, Fluorescence; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002374:Catalase; D000431:Ethanol; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban