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Neuropeptide Substance P Attenuates Hyperoxia-Induced Oxidative Stress Injury in Type II Alveolar Epithelial Cells Via Suppressing the Activation of JNK Pathway

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Abstract

Hyperoxia-induced oxidative stress plays a key role in many pulmonary diseases. In an earlier study we found the protective effect of the neuropeptide substance P (SP) on type II alveolar epithelial cells (AECIIs) after hyperoxia exposure. Then, we investigated c-Jun N-terminal kinase (C-JNK) signal transduction pathways in AECIIs before and after hyperoxia exposure. Primary AECIIs were isolated and purified from premature rats. Subsequently, the cells were treated with air (21% oxygen), hyperoxia (95% oxygen), SP+ air, and SP+ hyperoxia. SP was added in advance to reach a final concentration 1 × 10−6 mol/l. The cells were then exposed to air and hyperoxia for 12, 24, and 48 h. XTT cell proliferation assay and fluorescence-activated cell sorting (FACS) were employed to detect cell growth and apoptosis. Phosphorylated JNK (p-JNK) levels were measured using Western blot assay. The morphological alteration of AECIIs was observed using a transmission electron microscope (TEM). Compared with the simple hyperoxia treatment, the cell growth and apoptosis percentage was significantly increased and decreased after adding additional SP. Meanwhile, the reduced levels of p-JNKs could be found after adding SP. Furthermore, the morphological damage of AECIIs was greatly improved. These data suggest that SP can promote AECII proliferation and inhibit apoptosis by suppressing JNK signal pathways after hyperoxia exposure, which attenuates hyperoxia-induced oxidative stress damage in AECIIs. It might be a potential therapy for acute pulmonary injury under hyperoxia-induced oxidative stress.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 30572365).

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Authors and Affiliations

  1. Children’s Hospital of Chongqing Medical University, 136 Zhongshan No. 2 Road, Yu Zhong District, Chongqing, 400014, China

    Bo Huang, Hongmin Fu, Ming Yang, Fang Fang, Fengwu Kuang & Feng Xu

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  1. Bo Huang
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  2. Hongmin Fu
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  3. Ming Yang
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  4. Fang Fang
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Correspondence to Feng Xu.

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Huang, B., Fu, H., Yang, M. et al. Neuropeptide Substance P Attenuates Hyperoxia-Induced Oxidative Stress Injury in Type II Alveolar Epithelial Cells Via Suppressing the Activation of JNK Pathway. Lung 187, 421–426 (2009). https://doi.org/10.1007/s00408-009-9177-z

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