Palmitic Acid Methyl Ester Induces G2M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53p21 Pathway
Joint Authors
Sun, Li-Yi
Lin, Jian-Hong
Ting, Pei-Ching
Lee, Wen-Sen
Chiu, Hung-Wen
Chien, Chun-An
Liu, Chin-Hung
Yang, Kun-Ta
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-12-01
Country of Publication
Egypt
No. of Pages
15
Abstract EN
Bone marrow-derived mesenchymal cells (BM-MSCs) are able to differentiate into adipocytes, which can secrete adipokines to affect BM-MSC proliferation and differentiation.
Recent evidences indicated that adipocytes can secrete fatty acid metabolites, such as palmitic acid methyl ester (PAME), which is able to cause vasorelaxation and exerts anti-inflammatory effects.
However, effects of PAME on BM-MSC proliferation remain unclear.
The aim of this study was to investigate the effect of PAME on human BM-MSC (hBM-MSC) proliferation and its underlying molecular mechanisms.
hBM-MSCs were treated with PAME for 48 h and then subjected to various analyses.
The results from the present study show that PAME significantly reduced the levels of G2/M phase regulatory proteins, cyclin-dependent kinase 1 (Cdk1), and cyclin B1 and inhibited proliferation in hBM-MSCs.
Moreover, the level of Mdm2 protein decreased, while the levels of p21 and p53 protein increased in the PAME-treated hBM-MSCs.
However, PAME treatment did not significantly affect apoptosis/necrosis, ROS generation, and the level of Cdc25C protein.
PAME also induced intracellular acidosis and increased intracellular Ca2+ levels.
Cotreatment with PAME and Na+/H+ exchanger inhibitors together further reduced the intracellular pH but did not affect the PAME-induced decreases of cell proliferation and increases of the cell population at the G2/M phase.
Cotreatment with PAME and a calcium chelator together inhibited the PAME-increased intracellular Ca2+ levels but did not affect the PAME-induced cell proliferation inhibition and G2/M cell cycle arrest.
Moreover, the half-life of p53 protein was prolonged in the PAME-treated hBM-MSCs.
Taken together, these results suggest that PAME induced p53 stabilization, which in turn increased the levels of p53/p21 proteins and decreased the levels of Cdk1/cyclin B1 proteins, thereby preventing the activation of Cdk1, and eventually caused cell cycle arrest at the G2/M phase.
The findings from the present study might help get insight into the physiological roles of PAME in regulating hBM-MSC proliferation.
American Psychological Association (APA)
Lin, Jian-Hong& Ting, Pei-Ching& Lee, Wen-Sen& Chiu, Hung-Wen& Chien, Chun-An& Liu, Chin-Hung…[et al.]. 2019. Palmitic Acid Methyl Ester Induces G2M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53p21 Pathway. Stem Cells International،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1209572
Modern Language Association (MLA)
Lin, Jian-Hong…[et al.]. Palmitic Acid Methyl Ester Induces G2M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53p21 Pathway. Stem Cells International No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1209572
American Medical Association (AMA)
Lin, Jian-Hong& Ting, Pei-Ching& Lee, Wen-Sen& Chiu, Hung-Wen& Chien, Chun-An& Liu, Chin-Hung…[et al.]. Palmitic Acid Methyl Ester Induces G2M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53p21 Pathway. Stem Cells International. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1209572
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1209572