NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2.

Autor:	Zakaria MF; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan.; Department of Periodontology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan., Kato H; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan., Sonoda S; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan., Kato K; Department of Nursing, Fukuoka School of Health Sciences, Fukuoka 814-0005, Japan., Uehara N; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan., Kyumoto-Nakamura Y; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan., Sharifa MM; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan., Yu L; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan., Dai L; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan., Yamaza H; Department of Pediatric Dentistry, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan., Kajioka S; Department of Pharmacy in Fukuoka, International University of Health and Welfare, Okawa 831-8501, Japan., Nishimura F; Department of Periodontology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan., Yamaza T; Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka 812-8582, Japan.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2024 Oct 01; Vol. 137 (19). Date of Electronic Publication: 2024 Oct 10.
DOI:	10.1242/jcs.261732
Abstrakt:	Non-excitable cells express sodium voltage-gated channel alpha subunit 1 gene and protein (known as SCN1A and NaV1.1, respectively); however, the functions of NaV1.1 are unclear. In this study, we investigated the role of SCN1A and NaV1.1 in human mesenchymal stem cells (MSCs). We found that SCN1A was expressed in MSCs, and abundant expression of NaV1.1 was observed in the endoplasmic reticulum; however, this expression was not found to be related to Na+ currents. SCN1A-silencing reduced MSC proliferation and delayed the cell cycle in the S phase. SCN1A silencing also suppressed the protein levels of CDK2 and AKT (herein referring to total AKT), despite similar mRNA expression, and inhibited AKT phosphorylation in MSCs. A cycloheximide-chase assay showed that SCN1A-silencing induced CDK2 but not AKT protein degradation in MSCs. A proteolysis inhibition assay using epoxomicin, bafilomycin A1 and NH4Cl revealed that both the ubiquitin-proteasome system and the autophagy and endo-lysosome system were irrelevant to CDK2 and AKT protein reduction in SCN1A-silenced MSCs. The AKT inhibitor LY294002 did not affect the degradation and nuclear localization of CDK2 in MSCs. Likewise, the AKT activator SC79 did not attenuate the SCN1A-silencing effects on CDK2 in MSCs. These results suggest that NaV1.1 contributes to the cell cycle of MSCs by regulating the post-translational control of AKT and CDK2. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu