title: The dipyridyls paraquat and diquat attenuate the interaction of G-actin with thymosin beta4.
abstract: Beta-thymosins sequester G-actin and preserve a pool of monomers of actin which constitute an important prerequisite for cellular function of the microfilament system. To study the influence of paraquat binding to G-actin on the interaction of G-actin with thymosin beta4 we determined the apparent dissociation constant of the G-actin-thymosin beta4 complex in the absence or presence of paraquat using an ultrafiltration assay. Paraquat (1,1'-dimethyl-4,4'-dipyridylium dichloride) attenuates this interaction in a concentration- and time-dependent manner. When exposed to 10 mM paraquat, the apparent dissociation constant increased 10-85-fold within 15 min to 24 h. After incubation for 24 h even a paraquat concentration as low as 100 microM increased the dissociation constant of the G-actin-thymosin beta4 complex from 0.66 microM to 0.82 microM (P < 0.05). Diquat (1,1'-ethylene-2,2'-dipyridylium dibromide) similarly weakens the interaction of G-actin and beta-thymosins. In none of the experiments was oxidation of the methionine residue or any other modification of thymosin beta4 detected. Therefore we conclude that the dipyridyls paraquat and diquat directly interact with G-actin and thereby impede the interaction between G-actin and thymosin beta4.
authors.affiliation: Institut für Biochemie, Medizinische Fakultät, Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Huff
authors.forename: G
authors.initials: G
authors.lastname: Cappelletti
authors.forename: E
authors.initials: E
authors.lastname: Hannappel
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D004178:Diquat / Q000494:pharmacology*; D006540:Herbicides / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000737:chemistry; D010269:Paraquat / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013154:Spleen / Q000737:chemistry; D013947:Thymosin; D000099201:Thymosin beta(4)
chemical_list: D000199:Actins; D004178:Diquat; D006540:Herbicides; D010269:Paraquat; D013947:Thymosin; D000099201:Thymosin beta(4)