ABSTRACT
Two main isoforms of heme oxygenase (HO-1 and HO-2), the main enzyme of heme metabolism, were identified in the pineal gland. This suggests possible interactions between the melatonin synthesis pathway and the HO system. The aim of this study was to investigate the participation of carbon monoxide (CO), an HO by-product, on the melatonin synthesis pathway. Tests were carried using primary cell cultures of porcine pineal glands. The tricarbonyldichlororuthenium (II) dimer (CORM-2) compound was used as a CO donor at concentrations of 1 and 3 µM, as low concentrations of CORM-2 affect the regulation of the melatonin synthesis pathway in pineal cells in vitro. In addition, the presence of Sn-protoporphyrin-IX, an HO inhibitor, changed the melatonin response of pineal cells. These results suggest the existence of an intermediate mechanism in the pineal gland, which is associated with HO activity, that is involved in the modulation of melatonin synthesis.
Subject(s)
Carbon Monoxide , Melatonin/biosynthesis , Pineal Gland/metabolism , Animals , Heme Oxygenase (Decyclizing) , Heme Oxygenase-1 , SwineABSTRACT
Photoperiod is considered the most important factor entraining the circannual physiological rhythms through changing circadian patterns of melatonin (MEL) secretion from the pineal gland. The pineal gland of mammals does not respond directly to light but is controlled by light via neuronal phototransduction originating in the retina. In accordance with humoral phototransduction hypothesis, the aim of this study was to determine whether an increased concentration of CO, as a carrier of a light signal in pineal cell culture, affects the synthesis of melatonin. This study demonstrates that a commonly used carbon monoxide donor (CORM-2) markedly stimulated melatonin release from pineal cells incubated in vitro in a time-dependent manner, but the mechanism whereby CO modulates MEL release needs to be further explored.
