title: Effects of methylparathion on membrane fluidity and its implications for the mechanisms of toxicity.
abstract: As probed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 3-[p-(6-phenyl)-1,3,5-hexatrienyl] phenylpropionic acid (DPH-PA), methylparathion decreases the phase transition midpoint of dimyristoylphosphatidylcholine (DMPC) bilayers and broadens the transition profile. Furthermore, the insecticide orders to some extent the fluid phase of DMPC, in either the hydrophobic core or in the outer regions of the membrane, as evaluated by DPH and DPH-PA, respectively. These condensing effects of methylparathion were further confirmed in fluid models of egg-yolk phosphatidylcholine. The insecticide increases to some extent the ordering promoted by cholesterol in fluid bilayers of DMPC, but high cholesterol concentrations ( 30 mol%) prevent methylparathion interaction. In agreement with the data in models of synthetic lipids, the condensing effects of methylparathion in fluid native membranes of mitochondria, sarcoplasmic reticulum and erythrocytes are depressed with the increase in intrinsic cholesterol. Therefore, the effects of methylparathion are modulated, to a great extent, by membrane cholesterol concentration. Consequently, it can be suggested that the fluidity effects of methylparathion would be preferentially exerted in biomembranes scarce in cholesterol, e.g. mitochondria and sarcoplasmic reticulum. The perturbations promoted by methylparathion in these highly functional membranes will certainly induce bioenergetic alterations endangering cell and tissue functions, since membrane fluidity is a crucial parameter in the control of basic membrane mechanisms and, consequently, in cell homoeostasis.
authors.affiliation: Centro de Neurociências, Departamento de Zoologia, Universidade de Coimbra, 3049 Coimbra Codex, Portugal.
authors.forename: V I
authors.initials: VI
authors.lastname: Lopes
authors.forename: M C
authors.initials: MC
authors.lastname: Antunes-Madeira
authors.forename: V M
authors.initials: VM
authors.lastname: Madeira