[Goniodomin A induces modulation of actomyosin ATPase activity mediated through conformational change of actin].
Goniodomin A induced a potent stimulation of the actomyosin ATPase activities of actin-myosin reconstituted system and natural actomyosin. Interestingly, these stimulatory effects of goniodomin A were significantly inhibited by troponin-tropomyosin complex. The ATPase activity of skeletal muscle myofibrils and the contractile response of skinned fibers to Ca2+ were never activated and were decreased by this compound, suggesting inhibition by troponin-tropomyosin complex. In the analysis of the far-ultraviolet circular dichroism spectra, goniodomin A caused a concentration-dependent increase in alpha-helical content of actin. Goniodomin A inhibited the ATPase activities of atrial myofibrils, naural actimyosin and reconstituted actomyosin. Interestingly, these ATPase activities of ventricular muscle were enhanced by goniodomin A. The stimulatory effect of goniodomin A was significantly inhibited by troponin-tropomyosin complex. Goniodomin A increased the intracellular content of F-actin and caused the change in its distribution in 1321N1 cells. Goniodomin A-induced inositol phosphates accumulation in 1321N1 cells was reduced by C3 exoenzyme but was not affected by pertussis toxin. These results suggest that goniodomin A affects actin directly to modify the actin-myosin interaction and that goniodomin A-induced activation of the actomyosin ATPase activity may be physiologically significant because its activation is sensitive to the regulatory protein system, troponin-tropomyosin complex.
Matsunaga
K
K
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciiences, Tohoku University, Sendai, Japan.
Nakatani
K
K
Murakami
M
M
Nakahata
N
N
Ohizumi
Y
Y
D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002942:Circular Dichroism; D004789:Enzyme Activation; D004987:Ethers / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology*; D008387:Marine Toxins / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology; D009218:Myosins / Q000378:metabolism*; D011487:Protein Conformation; D011817:Rabbits; D014335:Tropomyosin; D014336:Troponin
D000199:Actins; D004987:Ethers; D007295:Inositol Phosphates; D018942:Macrolides; D008387:Marine Toxins; D014335:Tropomyosin; D014336:Troponin; C042260:troponin-tropomyosin complex; C059668:goniodomin A; D000251:Adenosine Triphosphatases; D009218:Myosins