NITRIC-OXIDE INDUCES CELL-DEATH IN A CATECHOLAMINERGIC CELL-LINE DERIVED FROM THE CENTRAL-NERVOUS-SYSTEM

The nitric oxide (NO) donors, sodium nitroprusside (SNP), noethyl)-N-( 2-ammonioethyl)amino]diazen-1-ium-1,2- diolate] (DETA NONOate), and S- nitroso-N-acetyl-D,L-penicillamine (SNAP) produce a dose-dependent inc rease in cell death in a catecholaminergic cell line (CATH.a) derived from the central nervous system. Cell death is associated with a decre ase in mitochondrial membrane potential. Dopamine also induced cell de ath of CATH.a cells and this was potentiated by concentrations of SNP which alone did not produce cell death. Hemoglobin, a scavenger of NO radicals, blocked SNP-and SNAP-induced cell death. Catalase and supero xide dismutase, enzymes that metabolize H2O2 and superoxide, respectiv ely, did not inhibit SNP- or SNAP-induced cell death. These data indic ate that NC) donors produce cell death in CATH.a cells through a mecha nism related to the production of NO and the loss of the mitochondrial membrane potential but unrelated to the production of H2O2. (C) 1998 Published by Elsevier Science Ireland Ltd.