Inhibition of actin polymerization by marine toxinpectenotoxin-2

The Journal of Veterinary Medical Science

Hiroshi OZAKI¹  Hideaki KARAKI¹  Masatoshi HORI¹  Ryo YOSHIMOTO¹  Yasuhiro MATSUURA¹  Takeshi YASUMOTO²  Futoshi YAZAMA³  Takeharu KANEDA⁴ 

[1] Department of Veterinary Pharmacology, Graduate Schoolof Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657,Japan;Japan Food Research Laboratories, 6-11-10 Nagayama,Tama, Tokyo 206-0025, Japan;Laboratory of Cell Biology and Morphology, School ofBioresources Hiroshima Prefectural University, Shoubara-shi, Hiroshima 727-0023,Japan;Laboratory of Veterinary Pharmacology, School ofVeterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho,Musashino, Tokyo 180-8602, Japan

关键词: actin depolymerization;    aorta;    macrolide;    marine toxin;    pectenotoxin;   

DOI  :  10.1292/jvms.17-0654

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

Pectenotoxin-2 (PCTX-2) is one of the polyether macrolide toxins isolated from scallopsinvolved in diarrheic shellfish poisoning via actin depolymerization. In the presentstudy, we examined the bioactive mechanism of PCTX-2 in smooth muscle cells and clarifymode of action of the PCTX-2-induced actin depolymerization using purified skeletal actin.PCTX-2 (300 nM-3 µM) non-selectively inhibited vascular smooth musclecontractions elicited by high K+ or phenylephrine in a dose-dependent manner.However, elevated cytosolic Ca2+ and myosin light chain phosphorylationstimulated by high K+ were only slightly inhibited by PCTX-2. By monitoring thefluorescent intensity of pyrenyl-actin, PCTX-2 was found to inhibit both the velocity anddegree of actin polymerization. The critical concentration of G-actin was linearlyincreased in accordance with the concentration of PCTX-2, indicating sequestration ofG-actin with 1 to 1 ratio. The kinetics of F-actin depolymerization by dilution assayindicated that PCTX-2 does not sever F-actin. Transmission electron microscopic andconfocal microscopic observations demonstrated that PCTX-2 selectively depolymerizedfilamentous actin without affecting tublin. In conclusion, PCTX-2 is a potent naturalactin depolymerizer which sequesters G-actin without severing F-actin.

【 授权许可】

Unknown