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Cyclic ADP ribose is a novel regulator of intracellular Ca2+ oscillations in human bone marrow mesenchymal stem cells.

Tao R, Sun HY, Lau CP, Tse HF, Lee HC, Li GR - J. Cell. Mol. Med. (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

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Effect of cADPR on cell proliferation in human MSCs. (A) Cyclic ADP ribose increased cell proliferation (assessed by MTT assay) in a concentration-dependent manner. The effect was antagonized by 100 μM 8-Br-cADPR. n = 10, *P < 0.05, **P < 0.01 versus 0 μM cADPR. (B) Cyclic ADP ribose increased 3H-thymidine incorporation in a concentration-dependent manner, and the effect was antagonized by 100 μM 8-Br-cADPR. n = 10, *P < 0.05, **P < 0.01 versus 0 μM cADPR. (C) Cyclic ADP ribose did not increase 3H-thymidine incorporation in cells transfected with TRMP2 siRNA A or B. n = 10, *P < 0.05 versus without cADPR application.
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fig06: Effect of cADPR on cell proliferation in human MSCs. (A) Cyclic ADP ribose increased cell proliferation (assessed by MTT assay) in a concentration-dependent manner. The effect was antagonized by 100 μM 8-Br-cADPR. n = 10, *P < 0.05, **P < 0.01 versus 0 μM cADPR. (B) Cyclic ADP ribose increased 3H-thymidine incorporation in a concentration-dependent manner, and the effect was antagonized by 100 μM 8-Br-cADPR. n = 10, *P < 0.05, **P < 0.01 versus 0 μM cADPR. (C) Cyclic ADP ribose did not increase 3H-thymidine incorporation in cells transfected with TRMP2 siRNA A or B. n = 10, *P < 0.05 versus without cADPR application.

Mentions: Cell proliferation was assessed by the MTT and the 3H-thymidine incorporation assays. Cyclic ADP ribose increased cell proliferation in a concentration-dependent manner and significant effects were observed at concentrations from 10 to 50 μM (Fig. 6A). At 50 μM, the cell proliferation was increased by 19 ± 7% as determined by the MTT assay. The effect was completely antagonized by co-administration of 100 μM 8-Br-cADPR (Fig. 6A). Likewise, 3H-thymidine incorporation was increased by cADPR in a concentration-dependent way. At 50 μM, DNA synthesis was enhanced by 32 ± 9% and the effect was fully countered by co-application of 8-Br-cADPR as well (Fig. 6B). Consistently, the increase in the rate of DNA synthesis by cADPR was not observed in cells transfected with the TRPM2 siRNAs (Fig. 6C), whereas the effect was still seen in the cells transfected with the control siRNA (n = 10, P < 0.01). These results indicate that the enhanced cell proliferation by cADPR is mediated by the TRPM2 channel.


Cyclic ADP ribose is a novel regulator of intracellular Ca2+ oscillations in human bone marrow mesenchymal stem cells.

Tao R, Sun HY, Lau CP, Tse HF, Lee HC, Li GR - J. Cell. Mol. Med. (2011)

Effect of cADPR on cell proliferation in human MSCs. (A) Cyclic ADP ribose increased cell proliferation (assessed by MTT assay) in a concentration-dependent manner. The effect was antagonized by 100 μM 8-Br-cADPR. n = 10, *P < 0.05, **P < 0.01 versus 0 μM cADPR. (B) Cyclic ADP ribose increased 3H-thymidine incorporation in a concentration-dependent manner, and the effect was antagonized by 100 μM 8-Br-cADPR. n = 10, *P < 0.05, **P < 0.01 versus 0 μM cADPR. (C) Cyclic ADP ribose did not increase 3H-thymidine incorporation in cells transfected with TRMP2 siRNA A or B. n = 10, *P < 0.05 versus without cADPR application.
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fig06: Effect of cADPR on cell proliferation in human MSCs. (A) Cyclic ADP ribose increased cell proliferation (assessed by MTT assay) in a concentration-dependent manner. The effect was antagonized by 100 μM 8-Br-cADPR. n = 10, *P < 0.05, **P < 0.01 versus 0 μM cADPR. (B) Cyclic ADP ribose increased 3H-thymidine incorporation in a concentration-dependent manner, and the effect was antagonized by 100 μM 8-Br-cADPR. n = 10, *P < 0.05, **P < 0.01 versus 0 μM cADPR. (C) Cyclic ADP ribose did not increase 3H-thymidine incorporation in cells transfected with TRMP2 siRNA A or B. n = 10, *P < 0.05 versus without cADPR application.
Mentions: Cell proliferation was assessed by the MTT and the 3H-thymidine incorporation assays. Cyclic ADP ribose increased cell proliferation in a concentration-dependent manner and significant effects were observed at concentrations from 10 to 50 μM (Fig. 6A). At 50 μM, the cell proliferation was increased by 19 ± 7% as determined by the MTT assay. The effect was completely antagonized by co-administration of 100 μM 8-Br-cADPR (Fig. 6A). Likewise, 3H-thymidine incorporation was increased by cADPR in a concentration-dependent way. At 50 μM, DNA synthesis was enhanced by 32 ± 9% and the effect was fully countered by co-application of 8-Br-cADPR as well (Fig. 6B). Consistently, the increase in the rate of DNA synthesis by cADPR was not observed in cells transfected with the TRPM2 siRNAs (Fig. 6C), whereas the effect was still seen in the cells transfected with the control siRNA (n = 10, P < 0.01). These results indicate that the enhanced cell proliferation by cADPR is mediated by the TRPM2 channel.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Show MeSH