Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death

被引：18

作者：

Fu, Hongmin ^{[1
]}

Zhang, Tiesong ^{[1
]}

Huang, Rongwei ^{[1
]}

Yang, Zhen ^{[1
]}

Liu, Chunming ^{[1
]}

Li, Ming ^{[1
]}

Fang, Fang ^{[2
]}

Xu, Feng ^{[2
]}

机构：

[1] Kunming Med Univ, Childrens Hosp, Dept Pediat Internal Med, Kunming 650032, Yunnan, Peoples R China

[2] Chongqing Med Univ, Childrens Hosp, Pediat Intens Care Unit, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China

来源：

EXPERIMENTAL AND THERAPEUTIC MEDICINE | 2017年 / 13卷 / 04期

基金：

中国国家自然科学基金;

关键词：

hyperoxia; alveolar epithelial type II cell; calcitonin gene-related peptide; acute lung injury; DNA damage; RESPIRATORY-DISTRESS-SYNDROME; LUNG INJURY; OXIDATIVE STRESS; REPAIR; OXYGEN; ACTIVATION; SECRETION; MORTALITY; EXPOSURE; TARGET;

D O I：

10.3892/etm.2017.4132

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Hyperoxia therapy for acute lung injury (ALI) may unexpectedly lead to reactive oxygen species (ROS) production and cause additional ALI. Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide that regulates inflammasome activation. However, the role of CGRP in DNA damage during hyperoxia is unclear. Therefore, the aim of the present study was to investigate the effects of CGRP on DNA damage and the cell death of alveolar epithelial type II cells (AEC II) exposed to 60% oxygen. AEC II were isolated from 19-20 gestational day fetal rat lungs and were exposed to air or to 60% oxygen during treatment with CGRP or the specific CGRP receptor antagonist CGRP(8-37). The cells were evaluated using immunofluorescence to examine surfactant protein-C and ROS levels were measured by probing with 2,7-dichlorofluorescin diacetate. The apoptosis rate and cell cycle of AEC II were analyzed by flow cytometry, and apoptosis was determined by western blotting analysis of activated caspase 3. The DNA damage was confirmed with immunofluorescence of H2AX via high-content analysis. The ROS levels, apoptotic cell number and the expression of H2AX were markedly increased in the hyperoxia group compared with those in the air group. Concordantly, ROS levels, apoptotic cell number and the expression of H2AX were significantly lower with a significant arrest of S and G2/M phases in the CGRP/O-2 group than in the hyperoxia or CGRP(8-37)/O-2 groups. CGRP was concluded to protect lung epithelium cells against hyperoxic insult, and upregulation of CGRP may be a possible novel therapeutic target to treat hyperoxic lung injury.

引用

页码：1279 / 1284

页数：6

共 37 条

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