Department of Foods and Nutrition, The University of Georgia, 425 River Road, Rhodes Center, Room 448, Athens, GA 30602-2771, USA.
Integr Biol (Camb). 2012 Aug;4(8):825-37. doi: 10.1039/c2ib20042b. Epub 2012 May 31.
Regucalcin was discovered in 1978 to be a calcium-binding protein that does not contain the EF-hand motif of the calcium-binding domain [M. Yamaguchi and T. Yamamoto, Chem. Pharm. Bull., 26, 1915-1918, 1978]. The regucalcin gene is localized on the X chromosome and its expression is enhanced through various transcription factors. Regucalcin is known to play a multifunctional role as a suppressor protein of cell signaling in many cell types. Regucalcin is expressed in rat brain neurons and it is decreased in the cerebral cortex and hippocampus of the brain with aging. Neuronal Ca(2+) signaling has been implicated in mechanisms of neuronal plasticity like long-term potentiation, which is likely to play an important role in learning and memory. The disturbance of brain Ca(2+) homeostasis may play a pivotal role in the revelation of brain disease. The intracellular Ca(2+) in brain tissues is increased with aging. Aging enhances the entry of Ca(2+) into brain neuronal cells across the plasma membranes. An increase in the brain microsomal Ca(2+)-ATPase activity of rats with aging resulted in calcium accumulation in the microsomes of the Ca(2+)-sequestrating system that is partly related to the brain toxicity by calcium. Regucalcin had an inhibitory effect on rat brain microsomal Ca(2+)-ATPase activity. The suppressive effect of regucalcin on brain microsomal Ca(2+)-ATPase activity was weakened in aged rats. Regucalcin was found to inhibit brain cytosolic protein kinase C. Brain microsomal Ca(2+)-ATPase activity was enhanced by protein kinase C in aged rats. Regucalcin could also inhibit activity of Ca(2+)/calmodulin-dependent protein kinase, protein phosphatase, and Ca(2+)/calmodulin-dependent nitric oxide synthase, which is linked to Ca(2+) signaling, in the cytosol of rat brain neurons. These inhibitory effects of regucalcin were weakened with aging. Regucalcin may play a pivotal role in the regulation of Ca(2+) signaling which is stimulated through a neurotransmitter in the brain neurons with aging.
钙调节蛋白于 1978 年被发现是一种不含钙结合域 EF 手模体的钙结合蛋白[M. Yamaguchi 和 T. Yamamoto，Chem. Pharm. Bull.，26，1915-1918，1978]。钙调节蛋白基因定位于 X 染色体上，其表达可通过多种转录因子增强。钙调节蛋白作为许多细胞类型中细胞信号的抑制蛋白，具有多功能作用。钙调节蛋白在大鼠脑神经元中表达，并随着年龄的增长在大脑皮层和海马体中减少。神经元 Ca2+信号已被牵连到神经元可塑性的机制中，如长时程增强，这可能在学习和记忆中发挥重要作用。脑 Ca2+稳态的紊乱可能在揭示脑部疾病中发挥关键作用。随着年龄的增长，脑组织中的细胞内 Ca2+增加。衰老增强 Ca2+通过质膜进入脑神经元细胞。衰老大鼠脑微粒体 Ca2+-ATP 酶活性的增加导致 Ca2+在 Ca2+螯合系统的微粒体中积累，这部分与钙引起的脑毒性有关。钙调节蛋白对大鼠脑微粒体 Ca2+-ATP 酶活性有抑制作用。衰老大鼠脑微粒体 Ca2+-ATP 酶活性的抑制作用减弱。发现钙调节蛋白抑制脑胞质蛋白激酶 C。蛋白激酶 C 可增强衰老大鼠脑微粒体 Ca2+-ATP 酶活性。钙调节蛋白还可以抑制 Ca2+/钙调蛋白依赖性蛋白激酶、蛋白磷酸酶和 Ca2+/钙调蛋白依赖性一氧化氮合酶的活性，这些酶与 Ca2+信号有关，存在于大鼠脑神经元的胞质溶胶中。随着年龄的增长，钙调节蛋白的这些抑制作用减弱。钙调节蛋白可能在衰老时通过脑神经元中的神经递质刺激的 Ca2+信号调节中发挥关键作用。
