Nicotera P, Orrenius S, Nilsson T, Berggren P O
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1990 Sep;87(17):6858-62. doi: 10.1073/pnas.87.17.6858.
Recent studies in our laboratory have revealed the existence of an ATP- and calmodulin-dependent Ca2+ uptake system in rat liver nuclei that can promote increases in the free Ca2+ concentration in the nuclear matrix. In the present investigation we show that liver nuclei possess a marked ability to sequester and buffer Ca2+, suggesting a potential role for the nucleus in the regulation of the cytosolic free Ca2+ concentration. In addition, we demonstrate that the intracellular messenger, inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3], stimulates the release of a fraction of the nuclear Ca2+ and transiently lowers the intranuclear free Ca2+ concentration. The Ins(1,4,5)P3-stimulated Ca2+ release is followed by Ca2+ reuptake into an inositol phosphate-insensitive nuclear compartment. Together, these results demonstrate that liver nuclei contain, at least, two Ca2+ pools, one of which is releasable by Ins(1,4,5)P3. These findings are consistent with a role for the nucleus in the modulation of the cytosolic free Ca2+ level by agonists and suggest that the control of the nuclear Ca2+ load by second messengers may participate in the regulation of intranuclear Ca2(+)-dependent processes by hormones and other agents.
我们实验室最近的研究揭示，大鼠肝细胞核中存在一种依赖三磷酸腺苷（ATP）和钙调蛋白的钙离子摄取系统，该系统可促使核基质中游离钙离子浓度升高。在本研究中，我们发现肝细胞核具有显著的螯合和缓冲钙离子的能力，这表明细胞核在调节胞质游离钙离子浓度方面可能发挥作用。此外，我们还证明，细胞内信使肌醇-1,4,5-三磷酸[Ins-(1,4,5)P3]可刺激一部分核内钙离子释放，并使核内游离钙离子浓度短暂降低。在Ins(1,4,5)P3刺激钙离子释放后，钙离子会重新摄取到对肌醇磷酸不敏感的核区室中。这些结果共同表明，肝细胞核至少含有两个钙离子池，其中一个可被Ins(1,4,5)P3释放。这些发现与细胞核在激动剂调节胞质游离钙离子水平中的作用相一致，并表明第二信使对核钙离子负荷的控制可能参与激素和其他因子对核内钙离子依赖性过程的调节。
