Resende R R, Adhikari A, da Costa J L, Lorençon E, Ladeira M S, Guatimosim S, Kihara A H, Ladeira L O
Department of Physics, Institute of Exact Sciences, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
Biochim Biophys Acta. 2010 Feb;1803(2):246-60. doi: 10.1016/j.bbamcr.2009.11.008. Epub 2009 Dec 1.
Spontaneous Ca(2+) events have been observed in diverse stem cell lines, including carcinoma and mesenchymal stem cells. Interestingly, during cell cycle progression, cells exhibit Ca(2+) transients during the G(1) to S transition, suggesting that these oscillations may play a role in cell cycle progression. We aimed to study the influence of promoting and blocking calcium oscillations in cell proliferation and cell cycle progression, both in neural progenitor and undifferentiated cells. We also identified which calcium stores are required for maintaining these oscillations. Both in neural progenitor and undifferentiated cells calcium oscillations were restricted to the G1/S transition, suggesting a role for these events in progression of the cell cycle. Maintenance of the oscillations required calcium influx only through inositol 1,4,5-triphosphate receptors (IP(3)Rs) and L-type channels in undifferentiated cells, while neural progenitor cells also utilized ryanodine-sensitive stores. Interestingly, promoting calcium oscillations through IP(3)R agonists increased both proliferation and levels of cell cycle regulators such as cyclins A and E. Conversely, blocking calcium events with IP(3)R antagonists had the opposite effect in both undifferentiated and neural progenitor cells. This suggests that calcium events created by IP(3)Rs may be involved in cell cycle progression and proliferation, possibly due to regulation of cyclin levels, both in undifferentiated cells and in neural progenitor cells.
在多种干细胞系中都观察到了自发性Ca(2+)事件，包括癌细胞系和间充质干细胞。有趣的是，在细胞周期进程中，细胞在从G(1)期向S期转变时会出现Ca(2+)瞬变，这表明这些振荡可能在细胞周期进程中发挥作用。我们旨在研究促进和阻断钙振荡对神经祖细胞和未分化细胞的细胞增殖及细胞周期进程的影响。我们还确定了维持这些振荡需要哪些钙库。在神经祖细胞和未分化细胞中，钙振荡都局限于G1/S期转变，这表明这些事件在细胞周期进程中发挥作用。维持振荡仅需要未分化细胞中通过肌醇1,4,5-三磷酸受体（IP(3)Rs）和L型通道的钙内流，而神经祖细胞还利用了对兰尼碱敏感的钙库。有趣的是，通过IP(3)R激动剂促进钙振荡会增加细胞增殖以及细胞周期调节因子如细胞周期蛋白A和E的水平。相反，用IP(3)R拮抗剂阻断钙事件在未分化细胞和神经祖细胞中会产生相反的效果。这表明由IP(3)Rs产生的钙事件可能参与细胞周期进程和增殖，这可能是由于在未分化细胞和神经祖细胞中对细胞周期蛋白水平的调节。
