Early activation of p160ROCK by pressure overload in rat heart.
We investigated the effects of acute pressure overload on activation of p160(ROCK) in rat myocardium. Constriction of transverse aorta, controlled to increase peak systolic pressure of ascending aorta by approximately 40 mmHg, induced a rapid association of RhoA with Dbl-3 and p160(ROCK). The binding of p160(ROCK) to RhoA was rapidly increased, peaking at 30 min (approximately 3.5-fold), but reduced to lower levels (approximately 1.9-fold) by 60 min of pressure overload. The activity of immunoprecipitated p160(ROCK) toward myosin light chain increased approximately 2.5-fold within 10 min but decreased to lower levels (approximately 1.6-fold) after 60 min of pressure overload. Confocal microscopic analysis indicated that pressure overload induced the formation of aggregates of p160(ROCK) and RhoA along the longitudinal axis of cardiac myocytes. Immunoelectron microscopic analysis showed that pressure overload induced the association of p160(ROCK) and RhoA to Z-line, T-tubule, and subsarcolemmal areas. The rapid activation of p160(ROCK) by pressure overload and its aggregation in subcellular structures involved in transmission of mechanical force suggest a role for this enzyme in the mechanobiochemical transduction in the myocardium.
Torsoni
Adriana S
AS
Department of Internal Medicine, School of Medicine, State University of Campinas, 13081-970 Campinas, SP, Brazil.
Fonseca
Priscila M
PM
Crosara-Alberto
Daniela P
DP
Franchini
Kleber G
KG
D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000601:surgery; D001794:Blood Pressure / Q000502:physiology*; D004789:Enzyme Activation; D006352:Heart Ventricles / Q000166:cytology; D006439:Hemodynamics; D047908:Intracellular Signaling Peptides and Proteins; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein