Neurogenic Potential of the 18-kDa Mitochondrial Translocator Protein (TSPO) in Pluripotent P19 Stem Cells

被引:5
|
作者
Gonzalez-Blanco, Laura [1 ,2 ]
Carlos Bermejo-Millo, Juan [1 ,2 ,3 ]
Oliveira, Gabriela [4 ]
Potes, Yaiza [1 ,2 ,3 ]
Antuna, Eduardo [1 ,2 ,3 ]
Menendez-Valle, Ivan [1 ,2 ,3 ]
Vega-Naredo, Ignacio [1 ,2 ,3 ]
Coto-Montes, Ana [1 ,2 ,3 ]
Caballero, Beatriz [1 ,2 ,3 ]
机构
[1] Univ Oviedo, Fac Med, Dept Morphol & Cell Biol, Julian Claveria S-N, Oviedo 33006, Spain
[2] Inst Invest Sanitaria Principado Asturias ISPA, Oviedo 33011, Spain
[3] Inst Neurociencias Principado Asturias INEUROPA, Oviedo 33006, Spain
[4] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3060197 Cantanhede, Portugal
关键词
TSPO; mitochondria; stem cells; neurogenesis; EMBRYONAL CARCINOMA-CELLS; 18; KDA; DIFFERENTIATION; DEATH; ACTIVATION; APOPTOSIS; MELATONIN; ACID;
D O I
10.3390/cells10102784
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The 18-kDa translocator protein (TSPO) is a key mitochondrial target by which different TSPO ligands exert neuroprotective effects. We assayed the neurogenic potential of TSPO to induce the neuronal differentiation of pluripotent P19 stem cells in vitro. We studied changes in cell morphology, cell proliferation, cell death, the cell cycle, mitochondrial functionality, and the levels of pluripotency and neurogenesis of P19 stem cells treated with the TSPO ligand, PK 11195, in comparison to differentiation induced by retinoid acid (RA) and undifferentiated P19 stem cells. We observed that PK 11195 was able to activate the differentiation of P19 stem cells by promoting the development of embryoid bodies. PK 11195 also induced changes in the cell cycle, decreased cell proliferation, and activated cell death. Mitochondrial metabolism was also enhanced by PK 11195, thus increasing the levels of reactive oxygen species, Ca2+, and ATP as well as the mitochondrial membrane potential. Markers of pluripotency and neurogenesis were also altered during the cell differentiation process, as PK 11195 induced the differentiation of P19 stem cells with a high predisposition toward a neuronal linage, compared to cell differentiation induced by RA. Thus, we suggest a relevant neurogenic potential of TSPO along with broad therapeutic implications.
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页数:17
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