Glutathione depletion triggers actin cytoskeleton changes via actin-binding proteins.

Zepeta-Flores N, Valverde M, Lopez-Saavedra A, Rojas E

Genetics and molecular biology1 Apr 2018Cited by 11 (Europe PMC)

PMID29870570PMCIDPMC6082235DOI10.1590/1678-4685-gmb-2017-0158PepBankPUB-29870570

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

No result from this study comes from a test of the peptide.

Natural levels measured4

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01LabEndogenous levelIn vitro (cells)Mechanism
In human neuroblastoma cells, glutathione depletion reduced thymosin beta‑4 gene expression at 24 hours.
In plain wordsIn cells, lowering glutathione reduced the activity of the cell's own thymosin beta‑4 gene after 24 hours.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseThymosin beta-4 gene expression at 24 hours of GSH depletion
Study
humann: not reported in source
Human neuroblastoma MSN cells with glutathione depletion by buthionine sulfoximine
Outcome group
Cytoskeleton and cell structure · Nervous system and cognition
Source sentences
Summary
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
1 context sentence(design, population, supporting numbers)
Summary · context
To test this hypothesis, we evaluate the effect of GSH depletion via buthionine sulfoximine (5 and 12.5 mM) in human neuroblastoma MSN cells.
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-2987057001
02LabEndogenous levelIn vitro (cells)Mechanism
In human neuroblastoma cells, glutathione depletion reduced thymosin beta‑4 protein levels at 24 hours.
In plain wordsIn cells, lowering glutathione reduced the cell's own thymosin beta‑4 protein after 24 hours.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseThymosin beta-4 protein level at 24 hours of GSH depletion
Study
humann: not reported in source
Human neuroblastoma MSN cells with glutathione depletion by buthionine sulfoximine
Outcome group
Cytoskeleton and cell structure · Nervous system and cognition
Source sentences
Summary
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
1 context sentence(design, population, supporting numbers)
Summary · context
To test this hypothesis, we evaluate the effect of GSH depletion via buthionine sulfoximine (5 and 12.5 mM) in human neuroblastoma MSN cells.
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-2987057002
03LabEndogenous levelIn vitro (cells)Mechanism
In human neuroblastoma cells, the reduced thymosin beta‑4 expression disappeared after 48 hours of glutathione depletion.
In plain wordsIn cells, the drop in the cell's own thymosin beta‑4 went away after 48 hours of lower glutathione.
Peptide
Thymosin beta-4 (human)
Outcome
No significant changeThymosin beta-4 expression at 48 hours of GSH depletion
Study
humann: not reported in source
Human neuroblastoma MSN cells with glutathione depletion by buthionine sulfoximine
Outcome group
Cytoskeleton and cell structure · Nervous system and cognition
Source sentences
Summary
however, this suppression disappears after 48 hours of treatment
1 context sentence(design, population, supporting numbers)
Summary · context
To test this hypothesis, we evaluate the effect of GSH depletion via buthionine sulfoximine (5 and 12.5 mM) in human neuroblastoma MSN cells.
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-2987057003
04LabEndogenous levelIn vitro (cells)Mechanism
In human neuroblastoma cells with depleted glutathione, thymosin beta‑4, profilin and gelsolin co-localized towards cytoplasmic projections.
In plain wordsIn cells with lower glutathione, the cell's own thymosin beta‑4 and two other proteins moved together to the cell extensions.
Peptide
Thymosin beta-4 (human)
Outcome
Not applicableCo-localization of thymosin beta-4, profilin and gelsolin
Study
humann: not reported in source
Human neuroblastoma MSN cells with glutathione depletion by buthionine sulfoximine
Outcome group
Cytoskeleton and cell structure · Nervous system and cognition
Source sentences
Summary
These changes were sufficient to trigger the co-localization of the three proteins towards cytoplasmic projections.
1 context sentence(design, population, supporting numbers)
Summary · context
To test this hypothesis, we evaluate the effect of GSH depletion via buthionine sulfoximine (5 and 12.5 mM) in human neuroblastoma MSN cells.
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-2987057004

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Version history

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Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

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