Cyclic ADP ribose is a novel regulator of intracellular Ca2+ oscillations in human bone marrow mesenchymal stem cells.
Bottom Line: However, cADPR had no effect on adipogenesis or osteogenesis in human MSCs.Our results indicate that cADPR is a novel regulator of Ca(2+) (i) oscillations in human MSCs.It permeates the cell membrane through the nucleoside transporters and increases Ca(2+) oscillation via activation of the TRPM2 channel, resulting in enhanced phosphorylation of ERK1/2 and, thereby, stimulation of human MSC proliferation.
Affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.Show MeSH
Mentions: To investigate whether TRPM2 channels participate in the cADPR-induced increase of Ca2+i oscillation frequency, two structurally different inhibitors of the channel, econazole (10 μM) and clotrimazole (10 μM) , were tested in human MSCs. Both showed no significant effect on the spontaneous Ca2+i oscillations, but both effectively prevented the increase of Ca2+i oscillation frequency induced by cADPR (Fig. 4B and C). The quantitative results are summarized in Figure 4D. RT-PCR (Fig. 4E) showed the presence of the mRNA for the full length form of TRPM2, TRPM2-L, but not short form, TRPM2-S, which was also confirmed by Western blot analysis (Fig. 4F) for protein expression in human MSCs. These results suggest that the increased Ca2+i oscillation frequency by cADPR is most likely mediated by the TRPM2 channels.
Affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.