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Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways

  • Authors:
    • Can Wei
    • Hong-Zhu Li
    • Yue-Hong Wang
    • Xue Peng
    • Hong-Jiang Shao
    • Hong-Xia Li
    • Shu-Zhi Bai
    • Xiao-Xiao Lu
    • Ling-Yun Wu
    • Rui Wang
    • Chang-Qing Xu
  • View Affiliations / Copyright

    Affiliations: Department of Pathophysiology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Department of Ultrasound, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China
    Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 39-46
    |
    Published online on: November 11, 2015
       https://doi.org/10.3892/ijmm.2015.2408
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Abstract

Pulmonary vascular remodeling is a significant pathological feature of hypoxia-induced pulmonary hypertension (HPH), while pulmonary artery smooth muscle cell (PASMC) proliferation plays a leading role in pulmonary vascular remodeling. Spermine (Sp), a polyamine, plays a critical role in periodic cell proliferation and apoptosis. The present study was conducted to observe the association between hypoxia-induced PASMC proliferation and polyamine metabolism, and to explore the effects of exogenous Sp on PASMC poliferation and the related mechanisms. In the present study, PASMCs were cultured with cobalt chloride (CoCl2) to establish a hypoxia model, and Sp at various final concentrations (0.1, 1, 10 and 100 µM) was added to the medium of PASMCs 40 min prior to the induction of hypoxia. Cell proliferation was measured by 3-(4,5-dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay, cell counting kit-8 assay and 5-bromo‑2'‑deoxyuridine (BrdU) incorporation assay. Cell cycle progression was determined by flow cytometry, and the protein expression levels of spermidine/spermine N1-acetyltransferase (SSAT; the key enzyme in the terminal degradation of polyamine), ornithine decarboxylase (ODC; the key enzyme of polyamine biosynthesis), cyclin D1 and p27 were measured by western blot analysis. The results revealed that the proliferation of the PASMCs cultured with CoCl2 at 50 µM for 24 h markedly increased. The expression of ODC was decreased and the expression of SSAT was increased in the cells under hypoxic conditions. Exogenous Sp at concentrations of 1 and 10 µM significantly inhibited hypoxia-induced PASMC proliferation, leading to cell cycle arrest at the G1/G0 phase. In addition, Sp decreased cyclin D1 expression, increased p27 expression, and suppressed the phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT); however, the above-metioned parameters were not markedly affected by Sp at concentrations of 0.1 or 100 µM. These results suggest that hypoxia disrupts polyamine metabolism, and Sp at concentrations of 1 and 10 µM inhibits the increase in human PASMC proliferation caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways. This study thus offer new insight into the prevention and treatment of HPH.
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Copy and paste a formatted citation
Spandidos Publications style
Wei C, Li H, Wang Y, Peng X, Shao H, Li H, Bai S, Lu X, Wu L, Wang R, Wang R, et al: Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways. Int J Mol Med 37: 39-46, 2016.
APA
Wei, C., Li, H., Wang, Y., Peng, X., Shao, H., Li, H. ... Xu, C. (2016). Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways. International Journal of Molecular Medicine, 37, 39-46. https://doi.org/10.3892/ijmm.2015.2408
MLA
Wei, C., Li, H., Wang, Y., Peng, X., Shao, H., Li, H., Bai, S., Lu, X., Wu, L., Wang, R., Xu, C."Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways". International Journal of Molecular Medicine 37.1 (2016): 39-46.
Chicago
Wei, C., Li, H., Wang, Y., Peng, X., Shao, H., Li, H., Bai, S., Lu, X., Wu, L., Wang, R., Xu, C."Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways". International Journal of Molecular Medicine 37, no. 1 (2016): 39-46. https://doi.org/10.3892/ijmm.2015.2408
Copy and paste a formatted citation
x
Spandidos Publications style
Wei C, Li H, Wang Y, Peng X, Shao H, Li H, Bai S, Lu X, Wu L, Wang R, Wang R, et al: Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways. Int J Mol Med 37: 39-46, 2016.
APA
Wei, C., Li, H., Wang, Y., Peng, X., Shao, H., Li, H. ... Xu, C. (2016). Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways. International Journal of Molecular Medicine, 37, 39-46. https://doi.org/10.3892/ijmm.2015.2408
MLA
Wei, C., Li, H., Wang, Y., Peng, X., Shao, H., Li, H., Bai, S., Lu, X., Wu, L., Wang, R., Xu, C."Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways". International Journal of Molecular Medicine 37.1 (2016): 39-46.
Chicago
Wei, C., Li, H., Wang, Y., Peng, X., Shao, H., Li, H., Bai, S., Lu, X., Wu, L., Wang, R., Xu, C."Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways". International Journal of Molecular Medicine 37, no. 1 (2016): 39-46. https://doi.org/10.3892/ijmm.2015.2408
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