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

ABSTRACT: The actin-sequestering protein thymosin beta-4 (T?4) 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 T?4 expression and cancer cell migration using HeLa cervical cancer cells. NO production and T?4 expression were increased in a hypoxic condition. The treatment with N-(?-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, enhanced the transcription of T?4 and cancer cell migration. SNAP-1-induced cell migration was decreased by the inhibition of T?4 with small interference (si) RNA. In a hypoxic condition, treatment with N(G)-monomethyl-L-arginine (L-NMMA), nitric oxide synthase (NOS) inhibitor, reduced T?4 transcriptional activity, and hypoxia-inducible factor (HIF)-1?. Hypoxia-induced cancer cell migration was also decreased by L-NMMA treatment. In a normoxic condition, T?4 transcriptional activity was decreased in the cells incubated in the presence of L-NMMA after co-transfection with T?4 promoter and GST-conjugated HIF-1?. Collectively, these results suggest that NO could regulate the expression of T?4 by direct or indirect effect of HIF-1? on T?4 promoter.

SUBMITTER: Ryu YK

PROVIDER: S-EPMC4182666 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Ryu Yun-Kyoung YK Kang Joo-Hyun JH Moon Eun-Yi EY

PloS one 20141001 10

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-Glu ...[more]

PMID: 25271630

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Project description:IntroductionSystemic sclerosis is an autoimmune disease characterized by tissue fibrosis and microangiopathy. Vascular changes such as a decrease in capillary density diminish blood flow and impair tissue oxygenation. Reliable ways to monitor disease activity and predict disease progression are desired in the process of patient selection for clinical trials and to optimize individual patient outcomes. Hypoxia-inducible factor-1 (HIF-1) is a dimeric protein complex that plays an integral role in the body's response to hypoxia. Our study aimed to investigate the potential abnormalities of HIF-1α plasma concentration and its possible association with disease activity and vascular abnormalities in patients with systemic sclerosis.MethodsBlood plasma levels of HIF-1α were measured in patients with systemic sclerosis (n = 50) and in healthy individuals (n = 30) using commercially available ELISA test kits.ResultsThe results showed a marked increase in HIF-1α levels in patients with systemic sclerosis (3.042 ng/ml [2.295-7.749]) compared to the control group (1.969 ng/ml [1.531-2.903] p < 0.01). Patients with diffuse cutaneous SSc (2.803 ng/ml, IQR 2.221-8.799) and limited cutaneous SSc (3.231 ng/ml, IQR 2.566-5.502) exhibited elevated serum HIF-1α levels compared to the control group (p < 0.01). We found a notable increase in HIF-1α plasma concentration in patients with an "active" pattern (6.625 ng/ml, IQR 2.488-11.480) compared to those with either an "early" pattern (2.739, IQR 2.165-3.282, p < 0.05) or a "late" pattern (2.983 ng/ml, IQR 2.229-3.386, p < 0.05). Patients with no history of digital ulcers had significantly higher levels of HIF-1α (4.367 ng/ml, IQR 2.488-9.462) compared to patients with either active digital ulcers (2.832 ng/ml, IQR 2.630-3.094, p < 0.05) or healed digital ulcers (2.668 ng/ml, IQR 2.074-2.983, p < 0.05).ConclusionsOur results indicate that HIF-1α may serve as a biomarker in assessing microcirculatory changes in individuals with systemic sclerosis.

Dataset Information

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

Publications

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

Similar Datasets

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