IN-VITRO EFFECT OF THE CYSTEINE METABOLITES HOMOCYSTEIC ACID, HOMOCYSTEINE AND CYSTEIC ACID UPON HUMAN NEURONAL CELL-LINES

Cysteine (CYS) is a non-essential amino acid which elicits excitotoxic properties via the N-methyl-D-aspartate (NMDA) subtype of the glutama te receptor. CYS levels are known to be elevated in association with n eurological disease such as Alzheimers Disease (AD) and Parkinsons Dis ease (PD). We have previously reported studies investigating the toxic ity of CYS and its major metabolite cysteinesulfinic acid (CSA) to hum an neuronal cell lines in vitro and in continuation of this we now rep ort the toxicity of other compounds (Homocysteic Acid, HCA; Homocystei ne, HCYS; and Cysteic Acid, CA) in the CYS metabolic pathway. Three ce ll lines, all of human origin and derived from separate discrete areas of the brain were used in the neurotoxicity assays. Lactate dehydroge nase (LDH) release was assayed as a measure of cell death. The cell li nes investigated showed varying degrees of toxic responses which were the reverse of those seen when they were exposed to CYS or CSA. The SK .N.SH (Neuroblastoma) cell line, which exhibits a high toxic response to CYS and CSA, gave a low toxic response to HCA and CA while the TE 6 71 (Medulloblastoma) cell line, which exhibits a low toxic response to CYS and CSA, showed a high toxic response to HCYS, HCA and CA. Howeve r, the U-87 MG (Glioblastoma) cell line, which has a median toxic resp onse to CYS and CSA, also has median response to HCYS, HCA and CA. The se results show that toxic responses are cell-type specific for CYS an d its metabolites and this may be reflected in the patterns of neurode generation observed in such diseases as AD and PD. HCYS is selectively toxic to medulloblastoma cells; this may explain why high HCYS levels result in neural tube defects in prenatal humans, where the same cell -type is involved. (C) 1998 Inter Press Inc.