Melatonin induces alterations in protein expression in the Xenopus laevis retina

The hormone melatonin is synthesized by pinealocytes and retinal photoreceptors with a diurnal rhythm. Melatonin produced in the retina at night is thought to exert local modulatory effects by binding to specific receptors in several different retinal cell types. The mechanisms by which melatonin influences circadian activity in retinal cells is poorly understood. Suppression of cyclic AMP synthesis appears to be a major signaling pathway in response to melatonin receptor binding in many tissues. A potential downstream consequence of melatonin-induced changes in cyclic AMP concentrations and protein phosphorylation is the up- or down-regulation of expression of specific genes. In this report, we examined the changes in expression levels of specific proteins in the neural retina and retinal pigment epithelium (RPE) in response to melatonin treatment, because both of these tissues express melatonin receptors. Neural retina and RPE isolated from the eyes of Xenopus laevis were treated with or without 1 microM melatonin for 6 hr, then the rapidly synthesized tissue proteins were radiolabeled by a 15 min incubation with 35S-methionine, and the proteins were subsequently analyzed by two-dimensional gel electrophoresis and autoradiography. In both the neural retina and RPE, the densities of some specific proteins were altered in response to melatonin treatment, and the few protein spots that were altered were distinct between the two tissues. These results support the concept that one function of melatonin may be to regulate the expression of specific genes and the consequent protein levels, and that the target genes may differ according to the cell or tissue type.