CXCL12 Regulates the Cholinergic Locus and CHT1 Through Akt Signaling Pathway.
نویسندگان
چکیده
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION Our results suggest that CXCL12 contributes to cholinergic gene expression via Akt signaling pathway.
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ورودعنوان ژورنال:
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
دوره 40 5 شماره
صفحات -
تاریخ انتشار 2016