Metal chelators reverse the action of hydrogen peroxide in rat luteal cells

Abstract

In rat luteal cells hydrogen peroxide (H 2O 2) interferes with the functional coupling of the luteinizing hormone (LH) receptor and blocks cAMP-dependent progesterone production. To test if this action of H 2O 2 is dependent on the generation of hydroxyl radicals, the effects of metal chelators and hydroxyl radical scavengers were evaluated. The heavy metal chelator O-phenanthroline prevented H 2O 2 inhibition of LH-sensitive cAMP and progesterone accumulation and depletion of ATP. Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) partially reversed inhibition of cAMP accumulation by H 2O 2 and completely prevented H 2O 2-induced ATP depletion, but had no effect on H 2O 2 inhibition of progesterone synthesis. Three other heavy metal chelators, deferoxamine, bathocuproinedisulfonic acid (BA) and penicillamine, as well as hydroxyl radical scavengers ethanol, thiourea and N-(2-mercaptopropiony1)glycine (MPG), had no effect on the luteolytic actions of H 2O 2. Differential effects of the chelators were probably due to differences in their cell permeability and subcellular compartmentalization. We conclude that metal chelators block the luteolytic actions of H 2O 2 by a mechanism probably linked to inhibition of hydroxyl radical generation.