The protective role of calcitonin gene-related peptide (CGRP) in high-glucose-induced oxidative injury in rat aorta endothelial cells

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2019-11, Vol.121, p.170121-170121, Article 170121
• Main Authors: Guo, Yanjun, Zhang, Qin, Chen, Huilu, Jiang, Yixuan, Gong, Ping
• Format: Article
• Language: English
• Subjects: Calcitonin gene-related peptide; Diabetes mellitus; Nitric oxide; Reactive oxygen species
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2019.170121

•CGRP alleviated the high-glucose-induced cell apoptosis while CGRP did not have an obvious impact on cell viability.•CGRP regulated NO production, NOS and Ang II mRNA expression under high glucose.•CGRP attenuated the high-glucose-stimulated intracellular ROS production.•CGRP could inhibit the activated ERK1/2-NOX4 and the translocation of p47phox under high glucose.•The role of CGRP under high glucose may be of greater significance than that under normal glucose. Endothelial dysfunction is considered to be an initial indicator in diabetes-induced macrovascular complications. Evidence has shown that CGRP is an important neuropeptide active in vascular system, especially in vasorelaxation. This study aimed to investigate the role of CGRP in high-glucose-induced endothelial dysfunction in rat aorta endothelial cells (RAECs). Quantitative-real time PCR and western blots were used to determine the efficiency of overexpression and interference of CGRP. After incubation with normal glucose (5.5 mM) or high glucose (33 mM), the cell viability and cell apoptosis were tested. Afterwards, the Nitric Oxide (NO) production, the mRNA expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and angiotensin II (Ang II) and the level of reactive oxygen species (ROS) were determined. The involvement of ERK1/2-NOX4 was determined through western blots and the translocation of p47phox was also observed via cell immunofluorescence. CGRP alleviated the high-glucose-induced cell apoptosis while CGRP did not have an obvious impact on cell viability. Meanwhile, CGRP increased the NO production as well as the eNOS mRNA expression and reversely decreased the stimulated expression of iNOS and Ang II by high glucose. In addition, CGRP attenuated the high-glucose-stimulated intracellular ROS production by ERK1/2-NOX4 and the translocation of p47phox. These results indicated the protective role of CGRP in high-glucose-induced oxidative injury in RAECs possibly through inhibiting ERK1/2-NOX4. Our findings might help to further understand the potential role and possible mechanism of CGRP in endothelial dysfunction caused by high glucose.