Reactive Oxygen Species Mediate Amplitude-Dependent Hypertrophic and Apoptotic Responses to Mechanical Stretch in Cardiac Myocytes
| Autor: | David R. Pimentel, Wilson S. Colucci, Deborah A. Siwik, Lei Xiao, Jay K. Amin, Jason Viereck, Patrick J. Pagano, Jennifer Oliver-Krasinski, Douglas B. Sawyer, Krishna Singh, Thomas A. Miller, Ragavendra R. Baliga, Jing Wang |
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| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Porphyrins Physiology Heart Ventricles Apoptosis Biology Tritium medicine.disease_cause Superoxide dismutase chemistry.chemical_compound Leucine Superoxides Proto-Oncogene Proteins Internal medicine Organometallic Compounds medicine Animals Myocyte RNA Messenger Cells Cultured bcl-2-Associated X Protein chemistry.chemical_classification Reactive oxygen species Superoxide Cytochrome c Free Radical Scavengers Hypertrophy Ethylenediamines Rats Cell biology Endocrinology Animals Newborn Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 chemistry biology.protein Stress Mechanical Reactive Oxygen Species Cardiology and Cardiovascular Medicine Atrial Natriuretic Factor Oxidative stress Signal Transduction |
| Zdroj: | Circulation Research. 89:453-460 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/hh1701.096615 |
| Popis: | Oxidative stress stimulates both growth and apoptosis in cardiac myocytes in vitro. We investigated whether oxidative stress mediates hypertrophy and apoptosis in cyclically stretched ventricular myocytes. Neonatal rat ventricular myocytes cultured on laminin-coated silastic membranes were stretched cyclically (1 Hz) at low (nominal 5%) and high (nominal 25%) amplitudes for 24 hours. Stretch caused a graded increase in superoxide anion production as assessed by superoxide dismutase (SOD)-inhibitable cytochrome c reduction or electron paramagnetic resonance spectroscopy. The role of reactive oxygen species (ROS) was assessed using the cell-permeable SOD/catalase mimetics Mn(II/III)tetrakis(1-methyl-4-peridyl) (MnTMPyP) and EUK-8. Stretch-induced increases in protein synthesis ( 3 H-leucine incorporation) and cellular protein content were completely inhibited by MnTMPyP (0.05 mmol/L) at both low and high amplitudes of stretch. In contrast, while MnTMPyP inhibited basal atrial natriuretic factor (ANF) mRNA expression, the stretch-induced increase in ANF mRNA expression was not inhibited by MnTMPyP. In contrast to hypertrophy, only high-amplitude stretch increased myocyte apoptosis, as reflected by increased DNA fragmentation on gel electrophoresis and an ≈3-fold increase in the number of TUNEL-positive myocytes. Similarly, only high-amplitude stretch increased the expression of bax mRNA. Myocyte apoptosis and bax expression stimulated by high-amplitude stretch were inhibited by MnTMPyP. Both low- and high-amplitude stretch caused rapid phosphorylation of ERK1/2, while high-, but not low-, amplitude stretch caused phosphorylation of JNKs. Activation of both ERK1/2 and JNKs was ROS-dependent. Thus, cyclic strain causes an amplitude-related increase in ROS, associated with differential activation of kinases and induction of hypertrophic and apoptotic phenotypes. |
| Databáze: | OpenAIRE |
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