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01-11-2017 | ORIGINAL ARTICLE

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Alters Cell Cycle Progression in Human Neuroblastoma Cell Lines

Authors: Rakesh Kumar Sharma, Eduardo Candelario-Jalil, Doris Feineis, Gerhard Bringmann, Bernd L. Fiebich, Ravi Shankar Akundi

Published in: Neurotoxicity Research | Issue 4/2017

Abstract

1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline, abbreviated as TaClo, is an endogenous neurotoxin capable of formation in the brain through the condensation of neuronal tryptamine with ingested exogenous toxins such as trichloroethylene or chloral hydrate. Due to its structural resemblance to 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), and similar ability to inhibit mitochondrial complex I, TaClo has been implicated in the etiology of Parkinson’s disease. Previous studies have shown the cytotoxicity of TaClo in various cell culture models. In this study, we were interested in identifying the early molecular events within the cell upon exposure to TaClo, a potent mitochondrial toxin. We found increased phosphorylation of 5′-adenosine monophosphate-activated protein kinase (AMPK), induction of autophagy, and a dependence on glycolysis as some of the downstream events to TaClo treatment. Furthermore, TaClo-treated cells undergo accelerated late proliferation but form daughter cells containing fewer neurites, leading to their eventual apoptosis. We also found that TaClo inhibits neuronal prostaglandin E₂ synthesis which may play an important role in synaptic plasticity. These results show that TaClo-mediated inhibition of mitochondrial complex I have multiple effects on cellular physiology which are in line with other mitochondrial effectors of Parkinson’s disease.

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Title: 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Alters Cell Cycle Progression in Human Neuroblastoma Cell Lines
Authors: Rakesh Kumar Sharma
Eduardo Candelario-Jalil
Doris Feineis
Gerhard Bringmann
Bernd L. Fiebich
Ravi Shankar Akundi
Publication date: 01-11-2017
Publisher: Springer US
Published in: Neurotoxicity Research / Issue 4/2017
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-017-9782-1

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1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Alters Cell Cycle Progression in Human Neuroblastoma Cell Lines

Abstract

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Springer Medicine

Abstract

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