The Anti-Apoptotic Effect of Regucalcin Is Mediated Through Multisignaling Pathways

Apoptosis. 2013 Oct;18(10):1145-53. doi: 10.1007/s10495-013-0859-x.

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 Ca(2+)-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 Ca(2+)-activated DNA fragmentation, Ca(2+)/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis*
  • Calcium-Binding Proteins / metabolism*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • DNA Fragmentation
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Isothiocyanates / pharmacology
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / metabolism
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Nitric Oxide Synthase / metabolism
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Isothiocyanates
  • RGN protein, human
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase
  • sulforafan