Cytotoxicity of 3-hydroxykynurenine in a neuronal hybrid cell line

CL Eastman, TR Guilarte - Brain research, 1989 - Elsevier
CL Eastman, TR Guilarte
Brain research, 1989Elsevier
Abstract The toxicity of 3-hydroxykynurenine (3HK), an endogenous tryptophan metabolite
which is markedly elevated in rat CNS tissue as a result of neonatal vitamin B-6 deficiency,
was investigated in a neuronally derived hybrid cell line (N18-RE-105). At concentrations in
excess of 100 μM, 3HK was toxic to greater than 85% of cultured cells over the course of 24
h. The time course of 3HK toxicity was studied in cultures exposed to 500 μM 3HK. Cell lysis
proceeded linearly to completion in 8–12 h, but the toxic effects of exposure for 2 h were …
Abstract
The toxicity of 3-hydroxykynurenine (3HK), an endogenous tryptophan metabolite which is markedly elevated in rat CNS tissue as a result of neonatal vitamin B-6 deficiency, was investigated in a neuronally derived hybrid cell line (N18-RE-105). At concentrations in excess of 100 μM, 3HK was toxic to greater than 85% of cultured cells over the course of 24 h. The time course of 3HK toxicity was studied in cultures exposed to 500 μM 3HK. Cell lysis proceeded linearly to completion in 8–12 h, but the toxic effects of exposure for 2 h were irreversible. 3HK was the most potently toxic among several related kynurenine metabolites tested. The toxic effects of 3HK exposure were markedly attenuated or abolished in the presence of either catalase or glutathione, indicating a role of oxidative stress in 3HK toxicity.
Elsevier