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

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

Content Provider	Springer Nature Link
Author	Sharma, Rakesh Kumar Candelario Jalil, Eduardo Feineis, Doris Bringmann, Gerhard Fiebich, Bernd L. Akundi, Ravi Shankar
Copyright Year	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 E$_{2}$ 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.
Starting Page	649
Ending Page	660
Page Count	12
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	32
Issue Number	4
e-ISSN	14763524
Language	English
Publisher	Springer US
Publisher Date	2017-07-18
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	TaClo Neurodegeneration Trichloroethylene Chloral hydrate Prostaglandin E2 Mitochondria Neurosciences Neurology Neurochemistry Pharmacology/Toxicology Neurobiology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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Endogenous alkaloids in man. 28. (1R, 3S))-1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide methanol solvate, a potential synthetic precursor to enantiomerically pure TaClo

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

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