Abstract P-573: EXTRINSIC CALCITONIN GENE-RELATED PEPTIDE INHIBITS HYPEROXIA-INDUCED ALVEOLAR EPITHELIAL TYPE-II CELLS APOPTOSIS, OXIDATIVE STRESS AND REACTIVE OXYGEN SPECIES PRODUCTION BY ENHANCING NOTCH 1 AND HERP EXPRESSION

Abstract

Aims & Objectives: This study investigated the effects of calcitonin gene- related peptide (CGRP) on AEC II cells exposed to hyperoxia. Methods Neonatal rat AEC II cells were isolated and identified by detecting surfactant protein C (SP-C). Three small in- terfering RNAs targeting Notch 1 were synthesized and transfected into AEC II. A hyperoxia-exposed AEC II cell injury model was established and was divided into 8 groups. MDA levels and SOD activity were examined using lipid peroxidation assay kits. Apoptosis and reactive oxygen species (ROS) production were evaluated using flow cytometry. Notch 1 mRNA expression was examined using RT-PCR. Homocysteine-induced endoplasmic reticulum protein (HERP) was examined using Western blot analysis. Results CGRP treatment significantly enhanced MDA levels and decreased SOD activity compared to hyperoxia-treated AEC II cells (P<0.05). CGRP treatment significantly inhibited hyperoxia-induced AEC II cell apoptosis, and significantly suppressed hyperoxia-induced ROS production compared to hyperoxia-treated AEC II cells (P<0.05) either undergoing γ secretase inhibitor or Notch RNAinterference. CGRP significantly triggered Notch 1 mRNA expression and significantly enhanced HERP expression compared to hyperoxia-treated AEC II cells (P<0.05) either undergoing γ secretase inhibitor or Notch RNA interference. Conclusions In AEC II cells, extrinsic peptide CGRP suppressed hyperoxia-induced apoptosis, oxidative stress, and ROS production, which may be triggered by Notch 1 and HERP signaling pathway.