The actin-sequestering protein thymosin beta-4 is a novel target of hypoxia-inducible nitric oxide and HIF-1α regulation.

Ryu YK, Kang JH, Moon EY

PloS one1 Oct 2014Cited by 2 (Europe PMC)

PMID25271630PMCIDPMC4182666DOI10.1371/journal.pone.0106532PepBankPUB-25271630

Summary

The actin-sequestering protein thymosin beta-4 (Tβ4) is involved in various cellular and physiological processes such as proliferation, motility, growth and metastasis. Nitric oxide (NO) promotes tumor invasiveness and metastasis by activating various enzymes. Herein, we investigated whether hypoxia-inducible NO regulates Tβ4 expression and cancer cell migration using HeLa cervical cancer cells. NO production and Tβ4 expression were increased in a hypoxic condition. The treatment with N-(β-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, enhanced the transcription of Tβ4 and cancer cell migration. SNAP-1-induced cell migration was decreased by the inhibition of Tβ4 with small interference (si) RNA. In a hypoxic condition, treatment with N(G)-monomethyl-L-arginine (L-NMMA), nitric oxide synthase (NOS) inhibitor, reduced Tβ4 transcriptional activity, and hypoxia-inducible factor (HIF)-1α. Hypoxia-induced cancer cell migration was also decreased by L-NMMA treatment. In a normoxic condition, Tβ4 transcriptional activity was decreased in the cells incubated in the presence of L-NMMA after co-transfection with Tβ4 promoter and GST-conjugated HIF-1α. Collectively, these results suggest that NO could regulate the expression of Tβ4 by direct or indirect effect of HIF-1α on Tβ4 promoter.

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

Results from this study7

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 HeLa cervical cancer cells, Tβ4 expression was increased in a hypoxic condition.
In plain wordsIn HeLa cancer cells, the cells' own thymosin beta‑4 expression rose in low oxygen.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseTβ4 expression in hypoxia
Study
humann: not reported in source
HeLa cervical cancer cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
NO production and Tβ4 expression were increased in a hypoxic condition.
1 context sentence(design, population, supporting numbers)
Summary · context
Herein, we investigated whether hypoxia-inducible NO regulates Tβ4 expression and cancer cell migration using HeLa cervical cancer 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-2527163001
02LabEndogenous levelIn vitro (cells)Mechanism
In HeLa cells, the nitric oxide donor SNAP-1 enhanced the transcription of Tβ4.
In plain wordsIn HeLa cancer cells, a nitric oxide donor raised the transcription of the cells' own thymosin beta‑4.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseTβ4 transcription after nitric oxide donor SNAP-1
Study
humann: not reported in source
HeLa cervical cancer cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
The treatment with N-(β-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, enhanced the transcription of Tβ4 and cancer cell migration.
1 context sentence(design, population, supporting numbers)
Summary · context
Herein, we investigated whether hypoxia-inducible NO regulates Tβ4 expression and cancer cell migration using HeLa cervical cancer 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-2527163002
03LabEndogenous levelIn vitro (cells)Mechanism
In hypoxic HeLa cells, the nitric oxide synthase inhibitor L-NMMA reduced Tβ4 transcriptional activity.
In plain wordsIn HeLa cells in low oxygen, a nitric oxide synthase blocker lowered activity of the cells' own thymosin beta‑4 gene.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTβ4 transcriptional activity with L-NMMA in hypoxia
Study
humann: not reported in source
HeLa cervical cancer cells
Comparator
Hypoxia without L-NMMA
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
In a hypoxic condition, treatment with N(G)-monomethyl-L-arginine (L-NMMA), nitric oxide synthase (NOS) inhibitor, reduced Tβ4 transcriptional activity, and hypoxia-inducible factor (HIF)-1α.
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-2527163005
04LabEndogenous levelIn vitro (cells)Mechanism
In normoxic HeLa cells co-transfected with the Tβ4 promoter and HIF-1α, L-NMMA decreased Tβ4 transcriptional activity.
In plain wordsIn HeLa cells under normal oxygen, a nitric oxide synthase blocker lowered activity of the cells' own thymosin beta‑4 gene.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTβ4 transcriptional activity with L-NMMA in normoxia after HIF-1α co-transfection
Study
humann: not reported in source
HeLa cervical cancer cells
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
In a normoxic condition, Tβ4 transcriptional activity was decreased in the cells incubated in the presence of L-NMMA after co-transfection with Tβ4 promoter and GST-conjugated HIF-1α.
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-2527163007

Studies that did not test the peptide alone3

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

05LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Efficacy outcome
In HeLa cells, the nitric oxide donor SNAP-1 enhanced cancer cell migration.
In plain wordsIn lab tests, a nitric oxide donor increased the migration of HeLa cancer cells.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseCancer cell migration after SNAP-1
Study
humann: not reported in source
HeLa cervical cancer cells
Outcome group
Tumor growth · Cancer
Source sentences
Summary
The treatment with N-(β-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, enhanced the transcription of Tβ4 and cancer cell migration.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-2527163003
06LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In HeLa cells, inhibition of Tβ4 with small interference RNA decreased SNAP-1-induced cell migration.
In plain wordsIn lab tests, silencing thymosin beta‑4 reduced the cell migration that a nitric oxide donor caused in HeLa cells.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseSNAP-1-induced migration after Tβ4 siRNA
Study
humann: not reported in source
HeLa cervical cancer cells
Outcome group
Tumor growth · Cancer
Source sentences
Summary
SNAP-1-induced cell migration was decreased by the inhibition of Tβ4 with small interference (si) RNA.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-2527163004
07LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Efficacy outcome
In HeLa cells, L-NMMA decreased hypoxia-induced cancer cell migration.
In plain wordsIn lab tests, a nitric oxide synthase blocker reduced the low-oxygen-driven migration of HeLa cancer cells.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseHypoxia-induced cell migration with L-NMMA
Study
humann: not reported in source
HeLa cervical cancer cells
Outcome group
Tumor growth · Cancer
Source sentences
Summary
Hypoxia-induced cancer cell migration was also decreased by L-NMMA treatment.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-2527163006

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

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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