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Neurotoxicity Research

, Volume 32, Issue 4, pp 649–660 | Cite as

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

  • Rakesh Kumar Sharma
  • Eduardo Candelario-Jalil
  • Doris Feineis
  • Gerhard Bringmann
  • Bernd L. Fiebich
  • Ravi Shankar AkundiEmail author
ORIGINAL ARTICLE

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.

Keywords

TaClo Neurodegeneration Trichloroethylene Chloral hydrate Prostaglandin E2 Mitochondria 

Notes

Acknowledgements

The technical assistance of Ulrike Gotzinger-Berger, Brigitte Gunter, and Raina Seupel is sincerely acknowledged. This work was supported in part by the EU grant QLK3-CT2000 00463 (to B.L.F.) and South Asian University Start Up fund (to R.S.A.). E.C.J was supported by the Alexander von Humboldt Foundation (Bonn, Germany).

Compliance with Ethical Standards

Conflict of Interests

The authors declare no competing financial interests.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Rakesh Kumar Sharma
    • 1
  • Eduardo Candelario-Jalil
    • 2
  • Doris Feineis
    • 3
  • Gerhard Bringmann
    • 3
  • Bernd L. Fiebich
    • 4
  • Ravi Shankar Akundi
    • 1
    • 5
    Email author
  1. 1.Neuroinflammation Research GroupSouth Asian UniversityNew DelhiIndia
  2. 2.Department of Neuroscience, McKnight Brain InstituteUniversity of FloridaGainesvilleUSA
  3. 3.Institute of Organic ChemistryUniversity of WürzburgWürzburgGermany
  4. 4.Department of PsychiatryUniversity of Freiburg Medical SchoolFreiburgGermany
  5. 5.Faculty of Life Sciences and BiotechnologySouth Asian UniversityNew DelhiIndia

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