About this item:
625 Views | 444 Downloads
Author Notes:
Email Address: m.yamaguchi@emory.edu
The author has no conflicts of interest.
Subjects:
Research Funding:
Regucalcin studies of the author was supported by a Grant-in-Aid for Scientific Research (C) No. 63571053, No. 02671006, No. 04671362, No. 06672193, No. 08672522, No. 10672048, No. 13672292 and No. 17590063 from the Ministry of Education, Science, Sports, and Culture, Japan.
Also, the author was awarded the Bounty of Encouragement Foundation in Pharmaceutical Research and the Bounty of the Yamanouchi Foundation for Research on Metabolic Disorders.
This study was also supported by the Foundation for Biomedical Research on Regucalcin.
Keywords:
- Regucalcin
- Apoptosis
- Calcium signaling
- Endonuclease
- Caspase-3 B
- Bci-2
- Nucleus
The anti-apoptotic effect of regucalcin is mediated through multisignaling pathways
Abstract:
Regucalcin (RGN/SMP30) was originally discovered in 1978 as a calcium-binding protein that does not contain the EF-hand motif of as a calcium-binding domain. The name, regucalcin, was proposed for this calcium-binding protein, which can regulate various Ca2+-dependent enzymes activation in liver cells. The regucalcin gene is localized on the X chromosome, and its expression is mediated through many signaling factors. Regucalcin plays a pivotal role in regulation of intracellular calcium homeostasis in various cell types. Regucalcin also has a suppressive effect on various signaling pathways from the cytoplasm to nucleus in proliferating cells and regulates nuclear function in including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis. Overexpression of endogenous regucalcin was found to suppress apoptosis in modeled rat hepatoma cells and normal rat kidney proximal epithelial NRK52 cells induced by various signaling factors. Suppressive effect of regucalcin on apoptosis is related to inhibition of nuclear Ca2+-activated DNA fragmentation, Ca2+/calmodulin-dependent nitric oxide synthase, caspase-3, Bax, cytochrome C, protein tyrosine kinase, protein tyrosine phosphatase in the cytoplasm and nucleus. Moreover, regucalcin stimulates Bcl-2 mRNA expression and depresses enhancement of caspase-3, Apaf-1 and Akt-1 mRNAs expression. This review discusses that regucalcin plays a pivotal role in rescue of apoptotic cell death, which is mediated through various signaling factors.
Copyright information:
© The Author(s) 2013
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits making multiple copies, distribution, public display, and publicly performance, distribution of derivative works, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.
