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Neuronal Apoptosis Induced by Pharmacological Concentrations of 3-Hydroxykynurenine : Characterization and Protection by Dantrolene and Bcl-2 Overexpression by Huafeng Wei; Peter Leeds; Ren-Wu Chen; Wenlin Wei; Yan Leng; Dale E. Bredesen; De-Maw Chuang is a Neuroscience article available to read on EtoBox.

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**Abstract** : We have studied neurotoxicity induced by pharmacological concentrations of 3‐hydroxykynurenine (3‐HK), an endogenous toxin implicated in certain neurodegenerative diseases, in cerebellar granule cells, PC12 pheochromocytoma cells, and GT1‐7 hypothalamic neurosecretory cells. In all three cell types, the toxicity was induced in a dose‐dependent manner by 3‐HK at high micromolar concentrations and had features characteristic of apoptosis, including chromatin condensation and internucleosomal DNA cleavage. In cerebellar granule cells, the 3‐HK neurotoxicity was unaffected by xanthine oxidase inhibitors but markedly potentiated by superoxide dismutase and its hemelike mimetic, MnTBAP [manganese(III) tetrakis(benzoic acid)porphyrin chloride]. Catalase blocked 3‐HK neurotoxicity in the absence and presence of superoxide dismutase or MnTBAP. The formation of H~2~O~2~ was demonstrated in PC12 and GT1‐7 cells treated with 3‐HK, by measuring the increase in the fluorescent product, 2′,7′‐dichlorofluorescein. In both PC12 and cerebellar granule cells, inhibitors of the neutral amino acid transporter that mediates the uptake of 3‐HK failed to block 3‐HK toxicity. However, their

Who reads Neuronal Apoptosis Induced by Pharmacological Concentrations of 3-Hydroxykynurenine : Characterization and Protection by Dantrolene and Bcl-2 Overexpression?

Author

Huafeng Wei; Peter Leeds; Ren-Wu Chen; Wenlin Wei; Yan Leng; Dale E. Bredesen; De-Maw Chuang

Publisher

John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 0022-3042)

Published

2000

Language

EN

Field

Neuroscience (Life Sciences)