Peroxynitrite induces F-actin depolymerization and blockade of myosin ATPase stimulation.
Treatment of F-actin with the peroxynitrite-releasing agent 3-morpholinosydnonimine (SIN-1) produced a dose-dependent F-actin depolymerization. This is due to released peroxynitrite because it is not produced by 'decomposed SIN-1', and it is prevented by superoxide dismutase concentrations efficiently preventing peroxynitrite formation. F-actin depolymerization has been found to be very sensitive to peroxynitrite, as exposure to fluxes as low as 50-100nM peroxynitrite leads to nearly 50% depolymerization in about 1h. G-actin polymerization is also impaired by peroxynitrite although with nearly 2-fold lower sensitivity. Exposure of F-actin to submicromolar fluxes of peroxynitrite produced cysteine oxidation and also a blockade of the ability of actin to stimulate myosin ATPase activity. Our results suggest that an imbalance of the F-actin/G-actin equilibrium can account for the observed structural and functional impairment of myofibrils under the peroxynitrite-mediated oxidative stress reported for some pathophysiological conditions.
Centre for Marine Sciences (CCMar), Depto. de Química e Bioquímica, FCT, Universidade do Algarve, 8005-139 Faro, Portugal.
Teresa
T
Tiago
Susana
S
Ramos
Manuel
M
Aureliano
Carlos
C
Gutiérrez-Merino
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002152:Calorimetry, Differential Scanning; D004789:Enzyme Activation / Q000187:drug effects; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009218:Myosins / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D011489:Protein Denaturation; D017510:Protein Folding; D011817:Rabbits; D013696:Temperature; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000199:Actins; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; C002385:linsidomine; D008981:Molsidomine; D009218:Myosins