H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2
| Autor: | Yuese Lin, Ling Zhu, Xinxue Liao, Shujuan Li, Yunquan Li, Xuandi Li, Huishen Wang, Guohui Liu, Dianqi Cai, Baoying Pan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Hypertension
Pulmonary Myocytes Smooth Muscle Prostaglandin Down-Regulation Sodium hydrosulfide Prostacyclin Biology Pulmonary Artery Sulfides medicine.disease_cause Cell Line chemistry.chemical_compound Downregulation and upregulation Genetics medicine Humans Familial Primary Pulmonary Hypertension Hydrogen Sulfide Cell Proliferation chemistry.chemical_classification Reactive oxygen species Cell growth General Medicine Cobalt Hydrogen Peroxide Molecular biology Epoprostenol Cell Hypoxia Acetylcysteine Oxidative Stress chemistry Apoptosis Cyclooxygenase 2 Reactive Oxygen Species Oxidative stress medicine.drug |
| Zdroj: | International journal of molecular medicine. 33(2) |
| ISSN: | 1791-244X |
| Popis: | 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 (H(2)S) all play an important role. In the present study, we aimed to examine the effects of H(2)S on the hypoxia-induced proliferation of human PASMCs (HPASMCs) and to elucidate the underlying mechanisms. The HPASMCs were treated with cobalt chloride (CoCl(2)), a hypoxia-mimicking agent, to establish a cellular model of hypoxic PAH. Prior to treatment with CoCl(2), the cells were pre-conditioned with sodium hydrosulfide (NaHS), a donor of H(2)S. Cell proliferation, reactive oxygen species (ROS) production, COX-2 expression, prostacyclin (also known as prostaglandin I2 or PGI(2)) secretion and H(2)S levels were detected in the cells. The exposure of the HPASMCs to CoCl(2) markedly increased cell proliferation, accompanied by a decrease in COX-2 expression, PGI(2) secretion and H(2)S levels; however, the levels of ROS were not altered. Although the exogenous ROS donor, H(2)O(2), triggered similar degrees of proliferation to CoCl(2), the ROS scavenger, N-acetyl-L-cysteine (NAC), markedly abolished the H(2)O(2)‑induced cell proliferation, as opposed to the CoCl(2)-induced proliferation. The CoCl(2)-induced proliferation of HPASMCs was suppressed by exogenously applied PGI(2). The addition of H(2)S (NaHS) attenuated the CoCl(2)-induced cell proliferation through the increase in the intercellular content of H(2)S. Importantly, the exposure of the cells to H(2)S suppressed the CoCl(2)-induced downregulation in COX-2 expression and PGI(2) secretion from the HPASMCs. In conclusion, the results from the current study suggest that H(2)S enhances hypoxia-induced cell proliferation through the upregulation of COX-2/PGI(2), as opposed to ROS. |
| Databáze: | OpenAIRE |
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