Effects of mitochondrial uncoupling protein 2 inhibition by Genipin on rat bone marrow mesenchymal stem cells under hypoxia and serum deprivation (H/SD) conditions.

Bone marrow-derived mesenchymal stem cells (BMSCs) have shown great promise for ischemic tissue repair. However, poor viability of transplanted BMSCs within ischemic tissues has limited their therapeutic potential. Numerous evidences suggested that reactive oxygen species (ROS) generated and apoptosis play an important role in regulation BMSCs loss at the ischemic site. Uncoupling protein 2 (UCP2), a member of the anion carrier superfamily of mitochondrial inner membrane and high expression in stem cells, has been reported to influence mitochondrial ROS production and regulate the energy metabolism. However the exact roles of UCP2 in regulation the BMSCs apoptosis are still not clear. In our study, we determined the functions of UCP2 in BMSCs from SD rats. Genipin, a special UCP2 inhibitor, was added into the cultural medium to reduce the UCP2 expression in BMSCs. Apoptosis was induced by the specific apoptotic insult hypoxia and serum deprivation (SD). There was no significant differences in ATP level in BMSCs from Genipin treatment group as compared with other treatment groups. But, the levels of Reactive oxygen species (ROS) and malondialdehyde (MDA) content in BMSCs treated with Genipin were significant higher than other groups (P<0.05). Furthermore, the level of BMSCs apoptosis was much higher in H/SD and 50 μM Genipin treatment group (31.93% ± 0.16) than H/SD treatment (17.59 ± 0.69) or control group (5.79 ± 0.04) (P<0.05). In addition, Bax and caspase3 activation were elevated after treatment with Genipin (P<0.05). However, the level of anti-apoptotic protein Bcl2 was significantly declined after treatment with Genipin (P<0.05). Taken together, our findings indicate that inhibitionof UCP2 by Genipin enhanced the BMSCs apoptosis under H/SD conditions.