NDLI: Aminochrome Toxicity is Mediated by Inhibition of Microtubules Polymerization Through the Formation of Adducts with Tubulin

Content Provider	Springer Nature Link
Author	Briceño, Andrea Muñoz, Patricia Brito, Patricia Huenchuguala, Sandro Segura Aguilar, Juan Paris, Irmgard B.
Copyright Year	2015
Abstract	In this study, we investigated the role of adducts formation between aminochrome and tubulin and its interference in microtubules assembly and stability in aminochrome-induced toxicity in SH-SY5Y cells. We also investigated whether changes in the microtubules structures are an early event that could affect tubulin expression. We demonstrated in vitro that aminochrome tubulin adducts inhibit tubulin polymerization and that aminochrome induces microtubules disassembly. Moreover, when the SH-SY5Y cells were incubated with aminochrome, we observed an increase in soluble tubulin, indicating depolymerization of microtubules. Aminochrome generates disruption of the microtubules network, leading to changes in the morphology of the cells inducing cell death, in a dose- and time-dependent manner. Interestingly, these changes preceded cell death and were partly inhibited by paclitaxel, a microtubule-stabilizing agent. Furthermore, we observed that aminochrome increased early tubulin expression before significant cell death occurred. Consequently, all these antecedents suggest that aminochrome toxicity is mediated by early disruption of microtubules network, where the adduct formation between aminochrome and tubulin could be responsible for the inhibition in the assembly microtubules and the loss of microtubules stability. Possibly, the early changes in tubulin expression could correspond to compensatory mechanisms against the toxic effects of aminochrome.
Starting Page	381
Ending Page	393
Page Count	13
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	29
Issue Number	3
e-ISSN	14763524
Language	English
Publisher	Springer US
Publisher Date	2015-09-07
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Aminochrome Tubulin Microtubules polymerization Parkinson’s disease Dopamine Neurodegeneration Neurosciences Neurology Neurochemistry Pharmacology/Toxicology Neurobiology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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