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. 2015:2015:867293.
doi: 10.1155/2015/867293. Epub 2015 Feb 18.

Coenzyme Q10 inhibits the aging of mesenchymal stem cells induced by D-galactose through Akt/mTOR signaling

Dayong Zhang  1 , Bingxi Yan  1 , Shanshan Yu  1 , Chong Zhang  1 , Baoming Wang  1 , Yayan Wang  1 , Junbo Wang  1 , Zhanggen Yuan  1 , Lihuang Zhang  1 , Jianping Pan  1
Affiliations

Coenzyme Q10 inhibits the aging of mesenchymal stem cells induced by D-galactose through Akt/mTOR signaling

Dayong Zhang et al. Oxid Med Cell Longev. 2015.

Abstract

Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10) plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal) can remarkably induce mesenchymal stem cell (MSC) aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling.

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Figures

Figure 1
Figure 1
Effects of different concentrations D-gal on MSCs senescence. (a) SA-β-gal staining. Compared with the control group, the number of SA-β-gal-positive cells in the 10 g/L D-gal and the 100 g/L D-gal group was clearly increased, and those SA-β-gal-positive cells show flat and enlarged cell shape. Scale bar = 25 μm. (b) Quantification of SA-β-gal-positive cells. The total number of SA-β-gal-positive cells among 100 random cells was counted using phase-contrast microscopy. The results showed that the number of SA-β-gal-positive MSCs/100 cells in the 10 g/L D-gal and the 100 g/L D-gal groups was significantly higher than that in the control group (* P < 0.01; n = 5).
Figure 2
Figure 2
Effects of different concentrations CoQ10 on MSCs senescence induced by D-gal. (a) SA-β-gal staining. In the 10 μmol/L CoQ10 and the 100 μmol/L CoQ10 groups, the number of SA-β-gal-positive cells was clearly decreased compared with that in the D-gal control group. Scale bar = 25 μm. (b) Quantification of SA-β-gal-positive cells. The total number of SA-β-gal-positive cells among 100 random cells was counted using phase-contrast microscopy. The results showed that the number of SA-β-gal-positive MSCs/100 cells in the 10 μmol/L CoQ10 and the 100 μmol/L CoQ10 groups was significantly lower than that in the D-gal control group (* P < 0.01; n = 5).
Figure 3
Figure 3
Effects of different concentrations CoQ10 on ROS generation in MSCs. (a) DCFH staining. In the 1, 10, and 100 μmol/L CoQ10 group, little DCFH-stained cells were observed under a fluorescence microscope compared with that in the D-gal control group. Green: DCFH staining; blue: Hoechst 33342 staining. Scale bar = 25 μm. (b) Quantification of intracellular ROS level. The DCFH fluorescence intensity in the 1, 10, and 100 μmol/L CoQ10 group was evidently lower compared with the D-gal control group (* P < 0.05, ** P < 0.01; n = 5). (c) MitoSOX staining. In the 1, 10, and 100 μmol/L CoQ10 group, MitoSOX fluorescence brightness was clearly lower than that in the D-gal control group. Red: MitoSOX staining; blue: Hoechst 33342 staining. Scale bar = 25 μm. (d) Quantification of mitochondrial ROS level. The MitoSOX fluorescence intensity in the 1, 10, and 100 μmol/L CoQ10 group was significantly lower compared with the control group (** P < 0.01; n = 5).
Figure 4
Figure 4
Effects of different concentrations CoQ10 on the expression of p16INK4a, p53, and p21 in MSCs. Protein expression of p16INK4a, p53, and p21 was examined by western blot. β-actin was used as the internal control. The p16INK4a, p53, and p21 expression levels were gradually lower in the 1, 10, and 100 μmol/L CoQ10 group compared with those in the D-gal control group.
Figure 5
Figure 5
Effects of CoQ10 on the expression of p-Akt and p-mTOR in MSCs. Western blot analysis of p-Akt and p-mTOR protein expression. β-actin was used as the internal control. The p-Akt and p-mTOR expression levels were gradually lower in the 1, 10, and 100 μmol/L CoQ 10 group compared with those in the D-gal control group.
Figure 6
Figure 6
Effects of Akt/mTOR signaling on MSC aging inhibited by CoQ10. (a) Western blot analysis. The p-Akt expression level was evidently higher in the CA-Akt group compared with that in the control group or the empty vector group. β-actin was used as the internal control. (b) Western blot analysis. The p-Akt, p-mTOR, p16INK4a, p53, and p21 expression levels were higher in the D-gal group compared with those in the control group. After treatment with CoQ10 in MSCs for 48 h, the p-Akt, p-mTOR, p16INK4a, p53, and p21 expression levels were lower compared with those in the D-gal group. However, in the D-gal + CoQ10 + CA-Akt group, the p-Akt, p-mTOR, p16INK4a, p53, and p21 expression levels were increased. β-actin was used as the internal control. (c) SA-β-gal staining. Compared with the control group, the number of SA-β-gal-positive cells in the D-gal group was clearly increased. In the D-gal + CoQ10 group, the number of SA-β-gal-positive cells was obviously decreased compared with that in the D-gal group. However, after constitutive overexpression of Akt, the number of SA-β-gal-positive cells in the D-gal + CoQ10 + CA-Akt group was clearly increased compared with the D-gal + CoQ10 group. Scale bar = 25 μm. (d) Quantification of SA-β-gal-positive cells. The total number of SA-b-gal-positive cells among 100 random cells was counted using phase-contrast microscopy. The results show that the number of SA-β-gal-positive MSCs/100 cells in the D-gal group was significantly higher than that in the control group (* P < 0.01; n = 3). In the D-gal + CoQ10 group, the number of SA-β-gal-positive cells was obviously decreased compared with that in the D-gal group (# P < 0.01; n = 3). In the D-gal + CoQ10 + CA-Akt group, the number of SA-β-gal-positive cells was clearly increased compared with the D-gal + CoQ10 group (§ P < 0.01; n = 3).
Figure 7
Figure 7
The proposed mechanism of CoQ10 in MSC aging induced by ROS.
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