1. Calcitonin gene-related peptide attenuates angiotensin II-induced ROS-dependent apoptosis in vascular smooth muscle cells by inhibiting the CaMKII/CREB signalling pathway
- Author
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Hong-Yu Sun, Wenxuan Liu, Liang-Yu Zhu, Xia Wu, Lu-Yao Wang, Lei Yang, and Hong-Min Luo
- Subjects
0301 basic medicine ,Vascular smooth muscle ,Calcitonin Gene-Related Peptide ,Biophysics ,Apoptosis ,Calcitonin gene-related peptide ,CREB ,Biochemistry ,Muscle, Smooth, Vascular ,03 medical and health sciences ,0302 clinical medicine ,Ca2+/calmodulin-dependent protein kinase ,Renin–angiotensin system ,Animals ,Humans ,Cyclic AMP Response Element-Binding Protein ,Molecular Biology ,Cells, Cultured ,chemistry.chemical_classification ,Reactive oxygen species ,integumentary system ,biology ,Chemistry ,Angiotensin II ,Cell Biology ,musculoskeletal system ,Cell biology ,030104 developmental biology ,nervous system ,030220 oncology & carcinogenesis ,cardiovascular system ,biology.protein ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,Reactive Oxygen Species ,Signal Transduction - Abstract
Apoptosis is associated with various cardiovascular diseases. CGRP exerts a variety of effects within the cardiovascular system, and protects against the onset and development of angiotensin (Ang) II-induced vascular dysfunction and remodelling. However, it is not known whether CGRP has a direct effect on Ang II-induced apoptosis in vascular smooth muscle cells (VSMCs), and the mechanism underlying the anti-apoptotic role remains unclear. In this study, CGRP significantly suppressed reactive oxygen species (ROS) and apoptosis in Ang II-induced VSMCs. In VSMCs pre-treated with a CGRP receptor antagonist (CGRP8-37), the CGRP-mediated inhibition of Ang II-induced ROS and apoptosis was completely abolished. Moreover, pre-treatment with N-acetyl-L cysteine (NAC), an ROS scavenger, blocked the effects of CGRP on Ang II-induced apoptosis. In addition, the activation of CaMKII and the downstream transcription factor CREB stimulated by Ang II was abrogated by CGRP. Importantly, in both CGRP and NAC-treated VSMCs, CGRP failed to further attenuate CaMKII and CREB activation. The results demonstrate that CGRP attenuated Ang II-induced ROS-dependent apoptosis in VSMCs by inhibiting the CaMKII/CREB signalling pathway.
- Published
- 2019