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Article

H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2

  • Authors:
    • Yunquan Li
    • Guohui Liu
    • Dianqi Cai
    • Baoying Pan
    • Yuese Lin
    • Xuandi Li
    • Shujuan Li
    • Ling Zhu
    • Xinxue Liao
    • Huishen Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Physiology, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China, Division II of General Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China, Department of Hypertension and Vascular Diseases, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China
  • Pages: 359-366
    |
    Published online on: December 9, 2013
       https://doi.org/10.3892/ijmm.2013.1579
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Abstract

The hypoxia-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main cause of pulmonary arterial hypertension (PAH), in which oxidative stress, cyclooxygenase (COX)-2 and hydrogen sulfide (H2S) all play an important role. In the present study, we aimed to examine the effects of H2S on the hypoxia-induced proliferation of human PASMCs (HPASMCs) and to elucidate the underlying mechanisms. The HPASMCs were treated with cobalt chloride (CoCl2), a hypoxia-mimicking agent, to establish a cellular model of hypoxic PAH. Prior to treatment with CoCl2, the cells were pre-conditioned with sodium hydrosulfide (NaHS), a donor of H2S. Cell proliferation, reactive oxygen species (ROS) production, COX-2 expression, prostacyclin (also known as prostaglandin I2 or PGI2) secretion and H2S levels were detected in the cells. The exposure of the HPASMCs to CoCl2 markedly increased cell proliferation, accompanied by a decrease in COX-2 expression, PGI2 secretion and H2S levels; however, the levels of ROS were not altered. Although the exogenous ROS donor, H2O2, triggered similar degrees of proliferation to CoCl2, the ROS scavenger, N-acetyl-L-cysteine (NAC), markedly abolished the H2O2‑induced cell proliferation, as opposed to the CoCl2-induced proliferation. The CoCl2-induced proliferation of HPASMCs was suppressed by exogenously applied PGI2. The addition of H2S (NaHS) attenuated the CoCl2-induced cell proliferation through the increase in the intercellular content of H2S. Importantly, the exposure of the cells to H2S suppressed the CoCl2-induced downregulation in COX-2 expression and PGI2 secretion from the HPASMCs. In conclusion, the results from the current study suggest that H2S enhances hypoxia-induced cell proliferation through the upregulation of COX-2/PGI2, as opposed to ROS.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Liu G, Cai D, Pan B, Lin Y, Li X, Li S, Zhu L, Liao X, Wang H, Wang H, et al: H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2. Int J Mol Med 33: 359-366, 2014.
APA
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X. ... Wang, H. (2014). H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2. International Journal of Molecular Medicine, 33, 359-366. https://doi.org/10.3892/ijmm.2013.1579
MLA
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X., Li, S., Zhu, L., Liao, X., Wang, H."H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2". International Journal of Molecular Medicine 33.2 (2014): 359-366.
Chicago
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X., Li, S., Zhu, L., Liao, X., Wang, H."H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2". International Journal of Molecular Medicine 33, no. 2 (2014): 359-366. https://doi.org/10.3892/ijmm.2013.1579
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Liu G, Cai D, Pan B, Lin Y, Li X, Li S, Zhu L, Liao X, Wang H, Wang H, et al: H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2. Int J Mol Med 33: 359-366, 2014.
APA
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X. ... Wang, H. (2014). H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2. International Journal of Molecular Medicine, 33, 359-366. https://doi.org/10.3892/ijmm.2013.1579
MLA
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X., Li, S., Zhu, L., Liao, X., Wang, H."H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2". International Journal of Molecular Medicine 33.2 (2014): 359-366.
Chicago
Li, Y., Liu, G., Cai, D., Pan, B., Lin, Y., Li, X., Li, S., Zhu, L., Liao, X., Wang, H."H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2". International Journal of Molecular Medicine 33, no. 2 (2014): 359-366. https://doi.org/10.3892/ijmm.2013.1579
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