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Issue 8, 2012
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Role of regucalcin in brain calcium signaling: involvement in aging

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Abstract

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 Ca2+ 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 Ca2+ homeostasis may play a pivotal role in the revelation of brain disease. The intracellular Ca2+ in brain tissues is increased with aging. Aging enhances the entry of Ca2+ into brain neuronal cells across the plasma membranes. An increase in the brain microsomal Ca2+-ATPase activity of rats with aging resulted in calcium accumulation in the microsomes of the Ca2+-sequestrating system that is partly related to the brain toxicity by calcium. Regucalcin had an inhibitory effect on rat brain microsomal Ca2+-ATPase activity. The suppressive effect of regucalcin on brain microsomal Ca2+-ATPase activity was weakened in aged rats. Regucalcin was found to inhibit brain cytosolic protein kinase C. Brain microsomal Ca2+-ATPase activity was enhanced by protein kinase C in aged rats. Regucalcin could also inhibit activity of Ca2+/calmodulin-dependent protein kinase, protein phosphatase, and Ca2+/calmodulin-dependent nitric oxide synthase, which is linked to Ca2+ 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 Ca2+ signaling which is stimulated through a neurotransmitter in the brain neurons with aging.

Graphical abstract: Role of regucalcin in brain calcium signaling: involvement in aging

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Publication details

The article was received on 27 Feb 2012, accepted on 27 Apr 2012 and first published on 01 May 2012


Article type: Review Article
DOI: 10.1039/C2IB20042B
Citation: Integr. Biol., 2012,4, 825-837
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    Role of regucalcin in brain calcium signaling: involvement in aging

    M. Yamaguchi, Integr. Biol., 2012, 4, 825
    DOI: 10.1039/C2IB20042B

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