Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway
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...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/7606238 |
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| author | Jian-Hong Lin Pei-Ching Ting Wen-Sen Lee Hung-Wen Chiu Chun-An Chien Chin-Hung Liu Li-Yi Sun Kun-Ta Yang |
| author_facet | Jian-Hong Lin Pei-Ching Ting Wen-Sen Lee Hung-Wen Chiu Chun-An Chien Chin-Hung Liu Li-Yi Sun Kun-Ta Yang |
| author_sort | Jian-Hong Lin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-12a7a73e2b764bf181b7f3e3019eaac1 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-12a7a73e2b764bf181b7f3e3019eaac12025-02-03T01:10:29ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/76062387606238Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 PathwayJian-Hong Lin0Pei-Ching Ting1Wen-Sen Lee2Hung-Wen Chiu3Chun-An Chien4Chin-Hung Liu5Li-Yi Sun6Kun-Ta Yang7PhD Program in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien, TaiwanDepartment of Surgery, Buddhist Tzu Chi General Hospital, No. 707, Sec. 3, Zhongyang Rd. Hualien, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wuxing St., Taipei, TaiwanMaster Program in Medical Physiology, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien, TaiwanDepartment of Molecular Biology and Human Genetics, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien, TaiwanDepartment of Pharmacology, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien, TaiwanGene and Stem Cell Manufacturing Center, Buddhist Tzu Chi General Hospital, No. 707, Sec. 3, Zhongyang Rd., Hualien, TaiwanMaster Program in Medical Physiology, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien, TaiwanBone 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.http://dx.doi.org/10.1155/2019/7606238 |
| spellingShingle | Jian-Hong Lin Pei-Ching Ting Wen-Sen Lee Hung-Wen Chiu Chun-An Chien Chin-Hung Liu Li-Yi Sun Kun-Ta Yang Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway Stem Cells International |
| title | Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway |
| title_full | Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway |
| title_fullStr | Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway |
| title_full_unstemmed | Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway |
| title_short | Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway |
| title_sort | palmitic acid methyl ester induces g2 m arrest in human bone marrow derived mesenchymal stem cells via the p53 p21 pathway |
| url | http://dx.doi.org/10.1155/2019/7606238 |
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