Send to

Choose Destination
Exp Ther Med. 2017 Apr;13(4):1279-1284. doi: 10.3892/etm.2017.4132. Epub 2017 Feb 16.

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

Author information

Department of Pediatric Internal Medicine, Children's Hospital, Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Pediatric Intensive Care Unit, Children's Hospital, Chongqing Medical University, Chongqing 400014, P.R. China.


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 CGRP8-37. 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 γH2AX were markedly increased in the hyperoxia group compared with those in the air group. Concordantly, ROS levels, apoptotic cell number and the expression of γH2AX were significantly lower with a significant arrest of S and G2/M phases in the CGRP/O2 group than in the hyperoxia or CGRP8-37/O2 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.


DNA damage; acute lung injury; alveolar epithelial type II cell; calcitonin gene-related peptide; hyperoxia

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center