title: Inhibitory effects of pectenotoxins from marine algae on the polymerization of various actin isoforms.
abstract: Pectenotoxins (PTXs) are marine toxins produced by dinoflagellates and which accumulate in shellfish. There are at least 14 different analogs of PTX with slight variations in structure leading to different chemical properties and consequently different toxicities. Since preliminary studies have shown that the parent compound PTX1 targets actin, we investigated the effects of two analogs, PTX2 and PTX2 seco acid, on the polymerization and depolymerization of skeletal muscle actin, smooth muscle actin, cardiac muscle actin, and non-muscle actin. Optimized actin assays using fluorescently labeled skeletal muscle actin and SDS-PAGE were jointly used to determine the relative amounts of filamentous and globular actin formed during polymerization and depolymerization experiments. Our findings suggest that PTX2 causes a dose-dependent decrease in both the rate and yield of skeletal muscle actin polymerization (IC50 values of 44 and 177 nM; respectively), with no significant effects on depolymerization. Moreover, the inhibitory effects of PTX2 are conserved towards other actin isoforms (i.e., smooth muscle, cardiac muscle, and non-muscle), as the inhibitory effects on actin polymerization were also observed with similar IC50 values (range: 19-94 nM). No inhibitory effects on polymerization were observed for PTX2 seco acid, suggesting an intact lactone ring is necessary for bioactivity.
authors.affiliation: Department of Natural Sciences, University of Michigan-Dearborn, Dearborn, MI 48128, USA.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Butler
authors.forename: Christopher O
authors.initials: CO
authors.lastname: Miles
authors.forename: Amna
authors.initials: A
authors.lastname: Karim
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Twiner
mesh_terms: D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D006801:Humans; D020128:Inhibitory Concentration 50; D018942:Macrolides; D058105:Polymerization / Q000187:drug effects*; D020033:Protein Isoforms; D011714:Pyrans / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D011817:Rabbits; D000095702:Polyether Toxins
chemical_list: D000199:Actins; D005663:Furans; D018942:Macrolides; D020033:Protein Isoforms; D011714:Pyrans; C420916:pectenotoxin-2-seco acid; D000095702:Polyether Toxins; C098380:pectenotoxin 2