Extracellular calcium induces neurite outgrowth through calcium-sensing receptors in PC12 HS cells

Yasushi Hasegawa * and Saori Toda

College of Environmental Technology, Muroran Institute of Technology, 27-1 Mizumoto, Muroran 050-8585, Japan.
 
Research Article
World Journal of Biology Pharmacy and Health Sciences, 2022, 11(03), 109–118.
Article DOI: 10.30574/wjbphs.2022.11.3.0128
Publication history: 
Received on 12 August 2022; revised on 24 September 2022; accepted on 26 September 2022
 
Abstract: 
PC12 cells have been used extensively to study neuronal differentiation and neurite outgrowth. However, the effects of extracellular Ca2+ on PC12 cells have not yet been sufficiently evaluated. In this study, we investigated the effect of extracellular calcium using PC12 HS cells, which have high sensitivity to nerve growth factor (NGF). The addition of Ca2+ (1 mM) to the medium induced neurite outgrowth and increased the intracellular calcium concentration. In contrast, the calcium-sensing receptor antagonist NPS2143 suppressed neurite outgrowth and increased the intracellular calcium concentration, suggesting that extracellular calcium promotes neurite outgrowth through calcium-sensing receptors. An increase in extracellular calcium concentration increased phosphorylation of Akt and cyclic AMP response element-binding protein (CREB). Semi-quantitative RT-PCR showed that elevated extracellular calcium increased the mRNA expression of brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor (PDGF), which are regulated by CREB activation. Our results suggest that elevated extracellular calcium can promote the phosphorylation of Akt and CREB through calcium-sensing receptors, resulting in the promotion of neurites. PC12 HS cells are a useful model to investigate the regulation of extracellular calcium via calcium-sensing receptors in neuronal cells.
 
Keywords: 
Calcium-sensing receptor; Extracellular calcium; Neurite extension; PC12HS
 
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