Inhibition of actin polymerization by marine toxin pectenotoxin-2

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Author(s)

    • HORI Masatoshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
    • YAZAMA Futoshi
    • Laboratory of Cell Biology and Morphology, School of Bioresources Hiroshima Prefectural University, Shoubara-shi, Hiroshima 727-0023, Japan
    • MATSUURA Yasuhiro
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
    • YOSHIMOTO Ryo
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
    • KANEDA Takeharu
    • Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo 180-8602, Japan
    • YASUMOTO Takeshi
    • Japan Food Research Laboratories, 6-11-10 Nagayama, Tama, Tokyo 206-0025, Japan
    • OZAKI Hiroshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
    • KARAKI Hideaki
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan

Abstract

<p>Pectenotoxin-2 (PCTX-2) is one of the polyether macrolide toxins isolated from scallops involved in diarrheic shellfish poisoning via actin depolymerization. In the present study, we examined the bioactive mechanism of PCTX-2 in smooth muscle cells and clarify mode of action of the PCTX-2-induced actin depolymerization using purified skeletal actin. PCTX-2 (300 nM-3 <i>µ</i>M) non-selectively inhibited vascular smooth muscle contractions elicited by high K<sup>+</sup> or phenylephrine in a dose-dependent manner. However, elevated cytosolic Ca<sup>2+</sup> and myosin light chain phosphorylation stimulated by high K<sup>+</sup> were only slightly inhibited by PCTX-2. By monitoring the fluorescent intensity of pyrenyl-actin, PCTX-2 was found to inhibit both the velocity and degree of actin polymerization. The critical concentration of G-actin was linearly increased in accordance with the concentration of PCTX-2, indicating sequestration of G-actin with 1 to 1 ratio. The kinetics of F-actin depolymerization by dilution assay indicated that PCTX-2 does not sever F-actin. Transmission electron microscopic and confocal microscopic observations demonstrated that PCTX-2 selectively depolymerized filamentous actin without affecting tublin. In conclusion, PCTX-2 is a potent natural actin depolymerizer which sequesters G-actin without severing F-actin.</p>

Journal

  • Journal of Veterinary Medical Science

    Journal of Veterinary Medical Science 80(2), 225-234, 2018

    JAPANESE SOCIETY OF VETERINARY SCIENCE

Codes

  • NII Article ID (NAID)
    130006339633
  • Text Lang
    ENG
  • ISSN
    0916-7250
  • Data Source
    J-STAGE 
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