The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review)

Yamaguchi,Masayoshi

doi:10.3892/ijmm.2015.2343

The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review)

Authors:
- Masayoshi Yamaguchi
View Affiliations

Affiliations: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Published online on: September 11, 2015 https://doi.org/10.3892/ijmm.2015.2343
Pages: 1191-1199

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The kidneys play a physiologic role in the regulation of urine formation and nutrient reabsorption in the proximal tubule epithelial cells. Kidney development has been shown to be regulated through calcium (Ca2+) signaling processes that are present through numerous steps of tubulogenesis and nephron induction during embryonic development of the kidneys. Ca2+-binding proteins, such as calbindin-D28k and regucalcin are important proteins that are commonly used as biomarkers in pronephric tubules, and the ureteric bud and metanephric mesenchyme. Previous research on regucalcin focused on Ca2+ sensors that are involved in renal organogenesis and the link between Ca2+-dependent signals and polycystins. Moreover, regucalcin has been highlighted to play a multifunctional role in kidney cell regulation. The regucalcin gene, which is localized on the X chromosome, is regulated through various transcription factors. Regucalcin has been found to regulate intracellular Ca2+ homeostasis in kidney proximal tubule epithelial cells. Regucalcin has been demonstrated to regulate the activity of various enzymes that are involved in intracellular signaling pathways. It has been noted that regucalcin suppresses DNA synthesis and regulates the gene expression of various proteins related to mineral transport, transcription factors, cell proliferation and apoptosis. The overexpression of regucalcin has been shown to exert suppressive effects on cell proliferation and apoptotic cell death, which are stimulated by various stimulatory factors. Moreover, regucalcin gene expression was found to to be involved in various pathophysiological states, including renal failure. This review discusses recent findings concerning the potential role of regucalcin as a regulatory protein in the kidney proximal tubule epithelial cells.

View Figures

View References

1	Gilbert T, Leclerc C and Moreau M: Control of kidney development by calcium ions. Biochimie. 93:2126–2131. 2011. View Article : Google Scholar : PubMed/NCBI
2	Yamaguchi M: Regucalcin, cell signaling-related protein: its multifunctional role in kidney cell regulation. OA Biotechnology. 1:22012. View Article : Google Scholar
3	Yamaguchi M: Role of regucalcin in calcium signaling. Life Sci. 66:1769–1780. 2000. View Article : Google Scholar : PubMed/NCBI
4	Yamaguchi M: Role of regucalcin in maintaining cell homeostasis and function (Review). Int J Mol Med. 15:371–389. 2005.PubMed/NCBI
5	Yamaguchi M: Regucalcin and cell regulation: role as a suppressor protein in signal transduction. Mol Cell Biochem. 353:101–137. 2011. View Article : Google Scholar : PubMed/NCBI
6	Yamaguchi M: The transcriptional regulation of regucalcin gene expression. Mol Cell Biochem. 346:147–171. 2011. View Article : Google Scholar
7	Yamaguchi M: Novel protein RGPR-p117: its role as the regucalcin gene transcription factor. Mol Cell Biochem. 327:53–63. 2009. View Article : Google Scholar : PubMed/NCBI
8	Shimokawa N and Yamaguchi M: Calcium administration stimulates the expression of calcium-binding protein regucalcin mRNA in rat liver. FEBS Lett. 305:151–154. 1992. View Article : Google Scholar : PubMed/NCBI
9	Yamaguchi M and Isogai M: Tissue concentration of calcium-binding protein regucalcin in rats by enzyme-linked immunoadsorbent assay. Mol Cell Biochem. 122:65–68. 1993. View Article : Google Scholar : PubMed/NCBI
10	Yamaguchi M and Kurota H: Expression of calcium-binding protein regucalcin mRNA in the kidney cortex of rats: the stimulation by calcium administration. Mol Cell Biochem. 146:71–77. 1995. View Article : Google Scholar : PubMed/NCBI
11	Yamaguchi M: Role of regucalcin in cell nuclear regulation: involvement as a transcription factor. Cell Tissue Res. 354:331–341. 2013. View Article : Google Scholar : PubMed/NCBI
12	Nakagawa T and Yamaguchi M: Hormonal regulation on regucalcin mRNA expression in cloned normal rat kidney proximal tubular epithelial NRK52E cells. J Cell Biochem. 95:589–597. 2005. View Article : Google Scholar : PubMed/NCBI
13	Sawada N and Yamaguchi M: Involvement of nuclear factor I-A1 in the regulation of regucalcin gene promoter activity in cloned normal rat kidney proximal tubular epithelial cells. Int J Mol Med. 18:665–671. 2006.PubMed/NCBI
14	Sawada N and Yamaguchi M: Overexpression of RGPR-p117 enhances regucalcin gene expression in cloned normal rat kidney proximal tubular epithelial cells. Int J Mol Med. 16:1049–1055. 2005.PubMed/NCBI
15	Sawada N and Yamaguchi M: Overexpression of RGPR-p117 enhances regucalcin gene promoter activity in cloned normal rat kidney proximal tubular epithelial cells: involvement of TTGGC motif. J Cell Biochem. 99:589–597. 2006. View Article : Google Scholar : PubMed/NCBI
16	van Os CH: Transcellular calcium transport in intestinal and renal epithelial cells. Biochim Biophys Acta. 906:195–222. 1987. View Article : Google Scholar : PubMed/NCBI
17	Taylor CW: Calcium regulation in vertebrates: an overview. Comp Biochem Physiol. 249–255. 1985. View Article : Google Scholar
18	Murata T and Yamaguchi M: Binding of kidney nuclear proteins to the 5′-flanking region of the rat gene for Ca²⁺-binding protein regucalcin: involvement of Ca²⁺/calmodulin signaling. Mol Cell Biochem. 199:35–40. 1999. View Article : Google Scholar : PubMed/NCBI
19	Verheijen MH and Defize LHK: Parathyroid hormone activates mitogen-activated protein kinase via a cAMP-mediated pathway independent of Ras. J Biol Chem. 272:3423–3429. 1997. View Article : Google Scholar : PubMed/NCBI
20	Liu Y, Yang Y, Ye YC, Shi QF, Chai K, Tashiro S, Onodera S and Ikejima T: Activation of ERK-p53 and ERK-mediated phosphorylation of Bcl-2 are involved in autophagic cell death induced by the c-Met inhibitor SU11274 in human lung cancer A549 cells. J Pharmacol Sci. 118:423–432. 2012. View Article : Google Scholar : PubMed/NCBI
21	Hunter T: Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 80:225–236. 1995. View Article : Google Scholar : PubMed/NCBI
22	Nakagawa T and Yamaguchi M: Overexpression of regucalcin suppresses cell response for tumor necrosis factor-α or transforming growth factor-β1 in cloned normal rat kidney proximal tubular epithelial NRK52E cells. J Cell Biochem. 100:1178–1190. 2007. View Article : Google Scholar
23	Kurota H and Yamaguchi M: Steroid hormonal regulation of calcium-binding protein regucalcin mRNA expression in the kidney cortex of rats. Mol Cell Biochem. 155:105–111. 1996. View Article : Google Scholar : PubMed/NCBI
24	van Heeswijk MPE, Geertsen JAM and van Os CH: Kinetic properties of the ATP-dependent Ca²⁺ pump and the Na⁺/Ca²⁺ exchange system in basolateral membranes from rat kidney cortex. J Membr Biol. 79:19–31. 1984. View Article : Google Scholar
25	Agus ZS, Chiu PJS and Goldberg M: Regulation of urinary calcium excretion in the rat. Am J Physiol. 232:F545–F549. 1977.PubMed/NCBI
26	Kurota H and Yamaguchi M: Activatory effect of calcium-binding protein regucalcin on ATP-dependent calcium transport in the basolateral membranes of rat kidney cortex. Mol Cell Biochem. 169:149–156. 1997. View Article : Google Scholar : PubMed/NCBI
27	Kurota H and Yamaguchi M: Regucalcin increases Ca²⁺-ATPase activity and ATP-dependent calcium uptake in the microsomes of rat kidney cortex. Mol Cell Biochem. 177:201–207. 1997. View Article : Google Scholar
28	Xue JH, Takahashi H and Yamaguchi M: Stimulatory effect of regucalcin on mitochondrial ATP-dependent calcium uptake activity in rat kidney cortex. J Cell Biochem. 80:285–292. 2000. View Article : Google Scholar : PubMed/NCBI
29	Nakagawa T, Sawada N and Yamaguchi M: Overexpression of regucalcin suppresses cell proliferation of cloned normal rat kidney proximal tubular epithelial NRK52E cells. Int J Mol Med. 16:637–643. 2005.PubMed/NCBI
30	Nakagawa T and Yamaguchi M: Overexpression of regucalcin enhances its nuclear localization and suppresses L-type Ca²⁺ channel and calcium-sensing receptor mRNA expressions in cloned normal rat kidney proximal tubular epithelial NRK52E cells. J Cell Biochem. 99:1064–1077. 2006. View Article : Google Scholar : PubMed/NCBI
31	Magno AL, Ward BK and Ratajczak T: The calcium-sensing receptor: a molecular perspective. Endocr Rev. 32:3–30. 2011. View Article : Google Scholar
32	Kennedy MB, Bennett MK, Erondu NE and Miller SG: Calcium/calmodulin-dependent protein kinases. Calcium and Cell function. Cheung WY: 7. Academic Press Inc; New York: pp. 61–107. 1987, View Article : Google Scholar
33	Kurota H and Yamaguchi M: Inhibitory effect of regucalcin on Ca²⁺/calmodulin-dependent protein kinase activity in rat renal cortex cytosol. Mol Cell Biochem. 177:239–243. 1997. View Article : Google Scholar
34	Kurota H and Yamaguchi M: Inhibitory effect of calcium-binding protein regucalcin on protein kinase C activity in rat renal cortex cytosol. Biol Pharm Bull. 21:315–318. 1998. View Article : Google Scholar : PubMed/NCBI
35	Pallen CJ and Wang JH: Calmodulin-stimulated dephosphorylation of p-nitrophenyl phosphate and free phosphotyrosine by calcineurin. J Biol Chem. 258:8550–8553. 1983.PubMed/NCBI
36	Omura M, Kurota H and Yamaguchi M: Inhibitory effect of regucalcin on Ca²⁺/calmodulin-dependent phosphatase activity in rat renal cortex cytosol. Biol Pharm Bull. 21:440–443. 1998. View Article : Google Scholar : PubMed/NCBI
37	Omura M and Yamaguchi M: Inhibition of Ca²⁺/calmodulin-dependent phosphatase activity by regucalcin in rat liver cytosol: involvement of calmodulin binding. J Cell Biochem. 71:140–148. 1998. View Article : Google Scholar : PubMed/NCBI
38	Morooka Y and Yamaguchi M: Suppressive role of endogenous regucalcin in the regulation of protein phosphatase activity in rat renal cortex cytosol. J Cell Biochem. 81:639–646. 2001. View Article : Google Scholar : PubMed/NCBI
39	Morooka Y and Yamaguchi M: Inhibitory effect of regucalcin on protein phosphatase activity in the nuclei of rat kidney cortex. J Cell Biochem. 83:111–120. 2001. View Article : Google Scholar : PubMed/NCBI
40	Morooka Y and Yamaguchi M: Endogenous regucalcin suppresses the enhancement of protein phosphatase activity in the cytosol and nucleus of kidney cortex in calcium-administered rats. J Cell Biochem. 85:553–560. 2002. View Article : Google Scholar : PubMed/NCBI
41	Yamaguchi M and Kurota H: Inhibitory effect of regucalcin on Ca²⁺/calmodulin-dependent cyclic AMP phosphodiesterase activity in rat kidney cytosol. Mol Cell Biochem. 177:209–214. 1997. View Article : Google Scholar
42	Lowenstein CJ, Dinerman JL and Snyder SH: Nitric oxide: a physiologic messenger. Ann Intern Med. 120:227–237. 1994. View Article : Google Scholar : PubMed/NCBI
43	Ma ZJ and Yamaguchi M: Regulatory effect of regucalcin on nitric oxide synthase activity in rat kidney cortex cytosol: Role of endogenous regucalcin in transgenic rats. Int J Mol Med. 12:201–206. 2003.PubMed/NCBI
44	Baba T and Yamaguchi M: Stimulatory effect of regucalcin on proteolytic activity in rat renal cortex cytosol: involvement of thiol proteases. Mol Cell Biochem. 195:87–92. 1999. View Article : Google Scholar : PubMed/NCBI
45	Baba T and Yamaguchi M: Stimulatory effect of regucalcin on proteolytic activity is impaired in the kidney cortex cytosol of rats with saline ingestion. Mol Cell Biochem. 206:1–6. 2000. View Article : Google Scholar : PubMed/NCBI
46	Croall DE and DeMartino GN: Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol Rev. 71:813–847. 1991.PubMed/NCBI
47	Nakagawa T and Yamaguchi M: Nuclear localization of regucalcin is enhanced in culture with protein kinase C activation in cloned normal rat kidney proximal tubular epithelial NRK52E cells. Int J Mol Med. 21:605–610. 2008.PubMed/NCBI
48	Morooka Y and Yamaguchi M: Suppressive effect of endogenous regucalcin on deoxyribonuclic acid synthesis in the nuclei of rat renal cortex. Mol Cell Biochem. 229:157–162. 2002. View Article : Google Scholar : PubMed/NCBI
49	Tsurusaki Y and Yamaguchi M: Role of regucalcin in liver nuclear function: Binding of regucalcin to nuclear protein or DNA and modulation of tumor-related gene expression. Int J Mol Med. 14:277–281. 2004.PubMed/NCBI
50	Charollais RH, Buquet C and Mester J: Butyrate blocks the accumulation of CDC2 mRNA in late G1 phase but inhibits both the early and late G1 progression in chemically transformed mouse fibroblasts BP-A31. J Cell Physiol. 145:46–52. 1990. View Article : Google Scholar : PubMed/NCBI
51	Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N, Inagaki M, Delcros JG and Moulinoux JP: Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem. 243:527–536. 1997. View Article : Google Scholar : PubMed/NCBI
52	Singh SV, Herman-Antosiewicz A, Singh AV, Lew KL, Srivastava SK, Kamath R, Brown KD, Zhang L and Baskaran R: Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. J Biol Chem. 279:25813–25822. 2004. View Article : Google Scholar : PubMed/NCBI
53	Park YC, Lee CH, Kang HS, Chung HT and Kim HD: Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, enhances LPS-induced NO production from murine peritoneal macrophages. Biochem Biophys Res Commun. 240:692–696. 1997. View Article : Google Scholar : PubMed/NCBI
54	Nakagawa T and Yamaguchi M: Overexpression of regucalcin suppresses apoptotic cell death in cloned normal rat kidney proximal tubular epithelial NRK52E cells: change in apoptosis-related gene expression. J Cell Biochem. 96:1274–1285. 2005. View Article : Google Scholar : PubMed/NCBI
55	Vogelstein B, Lane D and Levine AJ: Surfing the p53 network. Nature. 408:307–310. 2000. View Article : Google Scholar : PubMed/NCBI
56	Widmann C, Gibson S and Johnson GL: Caspase-dependent cleavage of signaling proteins during apoptosis. A turn-off mechanism for anti-apoptotic signals. J Biol Chem. 273:7141–7147. 1998. View Article : Google Scholar : PubMed/NCBI
57	Dieguez-Acuña FJ, Polk WW, Ellis ME, Simmonds PL, Kushleika JV and Woods JS: Nuclear factor kappaB activity determines the sensitivity of kidney epithelial cells to apoptosis: implications for mercury-induced renal failure. Toxicol Sci. 82:114–123. 2004. View Article : Google Scholar : PubMed/NCBI
58	Zhang YQ, Kanzaki M, Furukawa M, Shibata H, Ozeki M and Kojima I: Involvement of Smad proteins in the differentiation of pancreatic AR42J cells induced by activin A. Diabetologia. 42:719–727. 1999. View Article : Google Scholar : PubMed/NCBI
59	Hammar EB, Irminger JC, Rickenbach K, Parnaud G, Ribaux P, Bosco D, Rouiller DG and Halban PA: Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells. J Biol Chem. 280:30630–30637. 2005. View Article : Google Scholar : PubMed/NCBI
60	Fan JM, Ng YY, Hill PA, Nikolic-Paterson DJ, Mu W, Atkins RC and Lan HY: Transforming growth factor-β regulates tubular epithelial-myofibroblast transdifferentiation in vitro. Kidney Int. 56:1455–1467. 1999. View Article : Google Scholar : PubMed/NCBI
61	Shinya N, Kurota H and Yamaguchi M: Calcium-binding protein regucalcin mRNA expression in the kidney cortex is suppressed by saline ingestion in rats. Mol Cell Biochem. 162:139–144. 1996. View Article : Google Scholar : PubMed/NCBI
62	Shinya N and Yamaguchi M: Alterations in Ca²⁺-ATPase activity and calcium-binding protein regucalcin mRNA expression in the kidney cortex of rats with saline ingestion. Mol Cell Biochem. 170:17–22. 1997. View Article : Google Scholar : PubMed/NCBI
63	Shinya N and Yamaguchi M: Stimulatory effect of calcium administration on regucalcin mRNA expression is attenuated in the kidney cortex of rats ingested with saline. Mol Cell Biochem. 178:275–281. 1998. View Article : Google Scholar : PubMed/NCBI
64	Montine TJ and Borch RF: Role of endogenous sulfur-containing nucleophiles in an in vitro model of cis-diamminedichloroplatinum(II)-induced nephrotoxicity. Biochem Pharmacol. 39:1751–1757. 1990. View Article : Google Scholar : PubMed/NCBI
65	Goldstein RS, Pasino DA, Hewitt WR and Hook JB: Biochemical mechanisms of cephaloridine nephrotoxicity: time and concentration dependence of peroxidative injury. Toxicol Appl Pharmacol. 83:261–270. 1986. View Article : Google Scholar : PubMed/NCBI
66	Kurota H and Yamaguchi M: Suppressed expression of calcium-binding protein regucalcin mRNA in the renal cortex of rats with chemically induced kidney damage. Mol Cell Biochem. 151:55–60. 1995. View Article : Google Scholar : PubMed/NCBI
67	Misawa H and Yamaguchi M: Involvement of nuclear factor-1 (NF1) binding motif in the regucalcin gene expression of rat kidney cortex: the expression is suppressed by cisplatin administration. Mol Cell Biochem. 219:29–37. 2001. View Article : Google Scholar : PubMed/NCBI
68	Chiusolo A, Defazio R, Casartelli A, Bocchini N, Mongillo M, Zanetti E, Cristofori P and Trevisan A: Regucalcin down-regulation in rat kidney tissue after treatment with nephrotoxicants. Toxicol Lett. 182:84–90. 2008. View Article : Google Scholar : PubMed/NCBI
69	Arbillaga L, Vettorazzi A, Gil AG, van Delft JH, García-Jalón JA and López de Cerain A: Gene expression changes induced by ochratoxin A in renal and hepatic tissues of male F344 rat after oral repeated administration. Toxicol Appl Pharmacol. 230:197–207. 2008. View Article : Google Scholar : PubMed/NCBI
70	Wu HZ, Guo L, Mak YF, Liu N, Poon WT, Chan YW and Cai Z: Proteomics investigation on aristolochic acid nephropathy: a case study on rat kidney tissues. Anal Bioanal Chem. 399:3431–3439. 2011. View Article : Google Scholar
71	Klawitter J, Klawitter J, Kushner E, Jonscher K, Bendrick-Peart J, Leibfritz D, Christians U and Schmitz V: Association of immunosuppressant-induced protein changes in the rat kidney with changes in urine metabolite patterns: a proteo-metabonomic study. J Proteome Res. 9:865–875. 2010. View Article : Google Scholar
72	Murata T and Yamaguchi M: Alternatively spliced variants of the regucalcin gene in various human normal and tumor tissues. Int J Mol Med. 34:1141–1146. 2014.PubMed/NCBI