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 determine whether the cADPR-induced increase of proliferation is mediated by MAP kinases, we investigated the phosphorylated levels of the ERK1/2 and p38 MAP, and survival kinase Akt. Figure 7A shows that a 30-min incubation with cADPR (10 and 50 μM) increased the phosphorylation level of ERK1/2 (Thr185/Tyr187) in human MSCs, and the effect was countered by 8-Br-cADPR (Fig. 7A). The effect of cADPR on phosphorylated ERK1/2 was time dependent. The increase of ERK1/2 phosphrylation level was maximal at 60 min., and the effect remained significant at 180 min. (Fig. 7B). However, the increase of phosphorylated ERK1/2 by cADPR was remarkably reduced in the cells transfected with molecule A of TRPM2 siRNAs. Cyclic ADPR (50 μM, 60 min. incubation) only induced a slight increase of phosphorylated level of ERK1/2 in TRPM2 siRNA (n = 3, P = NS) (Fig. 7C).
Affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.