CXCL12 Regulates the Cholinergic Locus and CHT1 Through Akt Signaling Pathway.

Jing Yan, Wenhui Zhao, Meixia Guo, Xuefei Han, Zhiwei Feng

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2016

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CXCL12 is pivotal for cholinergic neurons, and it induces the expressions of several genes that are essential for synthesis and storage of acetylcholine(ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. The present study explored the impact of pharmacological Akt inhibition upon cholinergic gene expression. Western blotting was employed to determine the level of p-AKT, RT-PCR to check the mRNA levels of and CHT1(choline transporter1),VAChT and ChAT, ELISA to decipher the secretion of ACh and the activity of choline acetyltransferase. Here we demonstrated, in the rat pheochromocytoma cell line PC12 and in primary rat neuronal cultures, that CXCL12-evoked up-regulation of CHT1, VAChT and ChAT was mediated by Akt. Inhibition of Akt by the pharmacological inhibitor GSK690693 eliminated CXCL12-stimulated increases in cholinergic gene expression. Moreover, treatment with GSK690693 reversed CXCL12-evoked increases in choline acetyltransferase activity and ACh production. Our results suggest that CXCL12 contributes to cholinergic gene expression via Akt signaling pathway. © 2016 The Author(s) Published by S. Karger AG, Basel.

Citation

Jing Yan, Wenhui Zhao, Meixia Guo, Xuefei Han, Zhiwei Feng. CXCL12 Regulates the Cholinergic Locus and CHT1 Through Akt Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2016;40(5):982-992