Glutathione depletion triggers actin cytoskeleton changes via actin-binding proteins

Nahum Zepeta-Flores, Mahara Valverde, Alejandro López-Saavedra, Emilio Rojas

Research output: Contribution to journalArticle

Abstract

The importance of glutathione (GSH) in alternative cellular roles to the canonically proposed, were analyzed in a model unable to synthesize GSH. Gene expression analysis shows that the regulation of the actin cytoskeleton pathway is strongly impacted by the absence of GSH. To test this hypothesis, we evaluate the effect of GSH depletion via buthionine sulfoximine (5 and 12.5 mM) in human neuroblastoma MSN cells. In the present study, 70% of GSH reduction did not induce reactive oxygen species, lipoperoxidation, or cytotoxicity, which enabled us to evaluate the effect of glutathione in the absence of oxidative stress. The cells with decreasing GSH levels acquired morphology changes that depended on the actin cytoskeleton and not on tubulin. We evaluated the expression of three actin-binding proteins: thymosin β4, profilin and gelsolin, showing a reduced expression, both at gene and protein levels at 24 hours of treatment; however, this suppression disappears after 48 hours of treatment. These changes were sufficient to trigger the co-localization of the three proteins towards cytoplasmic projections. Our data confirm that a decrease in GSH in the absence of oxidative stress can transiently inhibit the actin binding proteins and that this stimulus is sufficient to induce changes in cellular morphology via the actin cytoskeleton.

Original languageEnglish (US)
Article numberS1415-47572018000300475
Pages (from-to)475-487
Number of pages13
JournalGenetics and Molecular Biology
Volume41
Issue number2
DOIs
StatePublished - Apr 1 2018

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Microfilament Proteins
Actin Cytoskeleton
Glutathione
Oxidative Stress
Profilins
Gelsolin
Thymosin
Buthionine Sulfoximine
Tubulin
Neuroblastoma
Reactive Oxygen Species
Proteins
Gene Expression

Keywords

  • BSO
  • Gelsolin
  • Glutathione
  • Profiling
  • Thymosin β4

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Glutathione depletion triggers actin cytoskeleton changes via actin-binding proteins. / Zepeta-Flores, Nahum; Valverde, Mahara; López-Saavedra, Alejandro; Rojas, Emilio.

In: Genetics and Molecular Biology, Vol. 41, No. 2, S1415-47572018000300475, 01.04.2018, p. 475-487.

Research output: Contribution to journalArticle

Zepeta-Flores, Nahum ; Valverde, Mahara ; López-Saavedra, Alejandro ; Rojas, Emilio. / Glutathione depletion triggers actin cytoskeleton changes via actin-binding proteins. In: Genetics and Molecular Biology. 2018 ; Vol. 41, No. 2. pp. 475-487.
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