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

Neurotoxicity Research
Andrea BriceñoIrmgard B Paris

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 fo...Continue Reading

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Citations

Mar 24, 2016·Cellular and Molecular Life Sciences : CMLS·Andrea HerreraJuan Segura-Aguilar
Jan 10, 2018·Neurotoxicity Research·Juan Segura-Aguilar
Jun 27, 2020·Neurotoxicity Research·Cleonice Creusa SantosVictor Diogenes Amaral Silva
Oct 22, 2018·Neurotoxicity Research·Sandro HuenchugualaJuan Segura-Aguilar
Aug 2, 2017·Neural Regeneration Research·Juan Segura-Aguilar
Mar 29, 2021·Redox Biology·David Ross, David Siegel

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