Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of regucalcin, a regulatory protein in intracellular signaling system, in the regulation of protein phosphatase activity in rat liver microsomes was investigated. Protein phosphatase activity torward phosphotyrosine, phosphoserine, and phosphothreonine was assayed in a reaction mixture containing the microsomal protein. Protein phosphatase activity toward phosphotyrosine was strong as compared with that of the enzyme activity toward phosphoserine and phosphothreonine, indicating the existence of protein tyrosine phosphatase. Protein phosphatase activity toward three phosphoaminoacids was significantly enhanced by the addition of both calcium chloride (10 micro M) and calmodulin (2.5 or 5 micro g/ml) in the reaction mixture. The presence of ethylene glycol bis (2-amino-ethylether) N, N, N', N'-tetracetic acid (EGTA; 0.1, 1 or 2 mM) or trifluoperazine (TFP; 10, 20 or 50 micro M), an antagonist of calmodulin, did not have a significant effect on protein phosphatase activity toward phosphotyrosine without calcium addition. Microsomal protein tyrosine phosphatase activity was not changed by okadaic acid (10(-6)-10(-4) M). The enzyme activity was significantly decreased by vanadate (10, 50 or 100 micro M). The addition of regucalcin (0.25 or 0.5 micro M) in the reaction mixture caused a significant inhibition of protein tyrosine phosphatase activity in liver microsomes. Western blot analysis showed a remarkable increase in regucalcin protein level in the liver microsomes of regucalcin transgenic (TG) rats. Protein tyrosine phosphatase activity was significantly suppressed in the liver microsomes of TG rats. This study demonstrates that protein tyrosine phosphatase activity is found in the liver microsomes, and that the enzyme activity is suppressed by regucalcin.
Int J Mol Med 2004 Sep
PMID:Characterization of protein tyrosine phosphatase activity in rat liver microsomes: suppressive effect of endogenous regucalcin in transgenic rats. 1528 95

Bone loss was previously shown to be induced in the femoral tissue of regucalcin transgenic (TG) rats. Regucalcin is expressed in rat bone marrow cells and its expression is enhanced in regucalcin TG rats. This study was undertaken to determine the change in osteoclastic bone resorption in regucalcin TG rats with increasing age. Femoral-diaphyseal and -metaphyseal tissues were obtained from normal (wild-type) and regucalcin TG rats aged 5, 14, 25 or 50 weeks. Calcium content in the femoral-diaphyseal and -metaphyseal tissues was significantly decreased in regucalcin TG male and female rats aged 5, 14, 25 or 50 weeks as compared with the value obtained from normal rats with each age. When the marrow cells obtained from normal or regucalcin TG rats were cultured for 7 days, the number of tartrate-resistant acid phosphatase (TRACP), a marker of osteoclasts, positive multinucleated cells (MNCs) were significantly increased in the marrow culture of regucalcin TG male and female rats aged 5, 14, 25 or 50 weeks. The effect of parathyroid hormone [human PTH (1-34); 10(-7) M] or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; 10(-7) M] in stimulating TRACP-positive MNC formation was significantly enhanced in regucalcin TG male and female rats aged 14 or 25 weeks. This study demonstrates that osteoclastic bone resorption is stimulated in regucalcin TG male and female rats with increasing age.
Int J Mol Med 2004 Sep
PMID:Bone loss in regucalcin transgenic rats: enhancement of osteoclastic cell formation from bone marrow of rats with increasing age. 1528 99

Regucalcin plays an important role as a regulatory protein in intracellular signaling pathway in many cells. Regucalcin transgenic (TG) rats have been shown to induce a remarkable increase in serum triglyceride and HDL-cholesterol concentrations at the age of 36 weeks (35). Furthermore, this was investigated in regucalcin TG rats with increasing age (14, 25, 36 or 50 weeks). Serum triglyceride or HDL-cholesterol concentration was markedly increased in regucalcin TG male and female rats at 14, 25, 36 or 50 weeks of age. Serum-free fatty acid concentration was significantly elevated in regucalcin TG male and female rats at 25, 36 or 50 weeks. In the TG female rats, a significant increase in serum free fatty acid concentration was also observed at 14 weeks of age, while it was not seen in the TG male rats. Serum-free cholesterol concentration was significantly increased in regucalcin TG female rats at 14, 25, 36 or 50 weeks. Such an increase was not induced in the TG male rats. Moreover, serum calcium concentration was significantly raised in regucalcin TG male and female rats at 50 weeks of age. Also, serum albumin concentration was significantly elevated in regucalcin TG female rats at 25, 36, or 50 weeks of age. Such an increase was not observed in the TG male rats. Serum zinc, glucose or urea nitrogen concentration was not significantly altered in TG male and female rats. This study demonstrates that hyperlipidemia is uniquely induced in regucalcin TG rats with increasing age.
Int J Mol Med 2004 Oct
PMID:Hyperlipidemia is induced in regucalcin transgenic rats with increasing age. 1537 96

The effect of regucalcin, a regulatory protein in the intracellular signaling system, on superoxide dismutase (SOD) activity in the heart cytosol of normal rats and regucalcin transgenic (TG) rats was investigated. The addition of regucalcin (10(-10) to 10(-8) M) with a physiologic concentration in the enzyme reaction mixture containing the heart cytosol obtained from normal rats caused a significant increase in SOD activity, indicating that regucalcin directly activates the enzyme. The effect of regucalcin (10(-8) M) in increasing SOD activity was not seen in the presence of dithiothreitol (DTT; 0.1 or 1.0 mM), a protecting reagent for sulfhydryl group, or N-ethylmaleimide (NEM; 0.1 or 1.0 mM), a modifying reagent for sulfhydryl group, in the reaction mixture, indicating that regucalcin does not affect the sulfhydryl group. The addition of zinc sulfate (10(-6) to 10(-4) M) in the reaction mixture did not cause a significant change in SOD activity, while the enzyme activity was markedly decreased in the presence of cupric sulfate (10(-6) to 10(-4) M). The activatory effect of regucalcin (10(-8) M) on SOD was seen in the presence of zinc (10(-4) M), while not observed in the presence of copper (10(-4) M). Moreover, SOD activity was significantly enhanced in the heart cytosol of regucalcin TG rats as compared with that of normal rats. This study demonstrates that regucalcin increases SOD activity in the heart cytosol of rats, and that its effect is not related to the sulfhydryl group of enzymes.
Int J Mol Med 2004 Oct
PMID:Regucalcin increases superoxide dismutase activity in the heart cytosol of normal and regucalcin transgenic rats. 1537 3

Many genes are expressed in mammalian liver in a sexually dimorphic manner. DNA microarray analysis has shown that growth hormone (GH) and its sex-dependent pattern of pituitary secretion play a major role in establishing the sexually dimorphic patterns of liver gene expression. However, GH may exert effects on protein post-translational modification and nuclear localization that are not reflected at the mRNA level. To investigate these potential effects of GH, we used two-dimensional gel electrophoresis followed by LC-MS/MS to: 1) identify rat liver nuclear proteins whose abundance or state of post-translational modification displays sex-dependent differences; and 2) determine the role of the plasma GH profile in establishing these differences. Nuclear extracts prepared from livers of individual male (n=9) and female (n=5) adult rats, and from males given GH by continuous infusion for 7 days to feminize liver gene expression (n=5 rats), were resolved by two-dimensional electrophoresis. Image analysis of SYPRO Ruby-stained gels revealed 165 sexually dimorphic protein spots that differ in normalized volume between male and female groups by >1.5-fold at p<0.05. Sixty of these proteins exhibited female-like changes in spot abundance following continuous GH treatment. Comparison of male and GH-treated male groups revealed 130 proteins that displayed >1.5-fold differences in abundance, with 60 of these GH-responsive spots being sexually dimorphic. Thus, GH plays an important role in establishing the sex-dependent differences in liver nuclear protein content. Twenty-eight of the sexually dimorphic and/or GH-regulated protein spots were identified by LC-MS/MS. Proteins identified include regucalcin, nuclear factor 45, and heterogeneous nuclear ribonucleoproteins A3, D-like, and K, in addition to proteins such as GST, normally associated with cytosolic extracts but also reported to be localized in the nucleus.
Mol Cell Proteomics 2004 Dec
PMID:Sexual dimorphism of rat liver nuclear proteins: regulatory role of growth hormone. 1545 55

The molecular cloning and sequencing of the cDNA coding for a novel regucalcin gene promoter region-related protein (RGPR-p117) from bovine, rabbit and chicken livers was investigated using rapid amplification of cDNA endo (RACE) method. Their nucleotide and amino acid sequences were compared with human, rat and mouse sequences published previously. RGPR-p117 of bovine, rabbit and chicken livers consisted of 1052, 1045, and 929 amino acid residues with calculated molecular mass of 117, 114, and 103 kDa, and estimated pI of 5.64, 5.84, and 5.59, respectively. Comparison analysis revealed that the nucleotide sequences of RGPR-p117 from mammalian species were highly-conserved in their coding region, and the homologies were at least 72.9%. The RGPR-p117 proteins in mammalian species consisted of 1045-1060 amino acids, and had 63.1-90.2% identity. Meanwhile, the nucleotide and amino acid sequences of chicken RGPR-p117 had at least 36.4 and 43.7% identities, respectively. Phylogenetic analysis showed that RGPR-p117 in six vertebrates appears to form a single cluster. Mammalian RGPR-p117 conserved a leucine zipper motif. Moreover, the analysis for subcellular localization of RGPR-p117 from six vertebrates showed the probability of nuclear localization >52.2%; the nuclear localization in rat and mouse was 78.3%. This study demonstrates a great conservation of RGPR-p117 genes throughout evolution.
Int J Mol Med 2005 Jan
PMID:A novel regucalcin gene promoter region-related protein: comparison of nucleotide and amino acid sequences in vertebrate species. 1558 34

Regucalcin was discovered in 1978 as a Ca(2+)-binding protein that does not contain EF-hand motif of Ca(2+)-binding domain. The name regucalcin was proposed for this Ca2(2+)binding protein, which can regulate liver cell functions related to Ca(2+). The regucalcin gene is localized on chromosome X, and the organization of the regucalcin gene consists of seven exons and six introns. AP-1 and NFI-A1 can bind to the promoter region of the rat regucalcin gene to mediate the Ca(2+) response for transcriptional activation. Regucalcin plays a pivotal role in maintaining intracellular Ca(2+) homeostasis due to activating Ca(2+) pump enzymes in the plasma membrane (basolateral membrane), microsomes (endoplasmic reticulum) and mitochondria of many cell types. Regucalcin has a suppressive effect on Ca(2+) signaling from the cytoplasm to the nucleus in the proliferative cells. Also, regucalcin has been demonstrated to transport to nucleus, and it can inhibit nuclear protein kinase, protein phosphatase, and deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis. Regucalcin can control enhancement of cell proliferation due to hormonal stimulation. Moreover, overexpression of regucalcin suppresses cell death and apoptosis in the cloned rat hepatoma cells induced by various signaling factors. Regucalcin plays a multifunctional role in the regulation of cellular function in liver, kidney cortex, heart and brain. Moreover, regucalcin-overexpressing rat has been shown to induce bone loss and hyperlipidemia with increasing age, indicating a pathophysiologic role. Regucalcin transgenic rat may be useful as an animal model in osteoporosis and hyperlipidemia. Thus, regucalcin plays a pivotal role in maintaining cell homeostasis and function. Regucalcin gene expression-related diseases may be found in human.
Int J Mol Med 2005 Mar
PMID:Role of regucalcin in maintaining cell homeostasis and function (review). 1570 26

The effect of regucalcin, a regulatory protein in intracellular signaling system, on cell death and apoptosis was investigated. Sulforaphane, a naturally occurring isothiocyanate, is known to induce cell cycle arrest and apoptosis in cancer cells, although its effect has not been clarified in the cloned rat hepatoma H4-II-E cells. Hepatoma H4-II-E cells (wild-type) and stable regucalcin/pCXN2-transfected cells were cultured for 72 h in a medium containing 10% fetal bovine serum (FBS). Cells with subconfluency were changed to a medium containing either vehicle or sulforaphane (10(-7) or 10(-6) M) in the absence of FBS. After medium change, cells were cultured for 24, 48, or 72 h. The number of wild-type cells was significantly decreased in the presence of sulforaphane (10(-7) or 10(-6) M). Agarose gel electrophoresis showed the presence of low-molecular-weight deoxyribonucleic acid (DNA) fragments of adherent wild-type cells cultured with sulforaphane (10(-7) or 10(-6) M) for 24 h. Sulforaphane (10(-7) or 10(-6) M)-induced cell number and DNA fragmentation was significantly suppressed in transfectants. The effect of sulforaphane (10(-6) M) in decreasing the number of wild-type cells was significantly prevented in the presence of caspase-3 inhibitor (10(-9) M), while the presence of Nomega-nitro-L-arginine methylester (NAME), an inhibitor of nitric oxide synthase, did not prevent sulforaphane-induced death of wild-type cells. Sulforaphane (10(-6) M) did not have a significant effect on cell number of transfectants in the presence of caspase-3 inhibitor or NAME. This study demonstrates that sulforaphane induces cell death and apoptosis in the cloned rat hepatoma H4-II-E cells, and that overexpression of regucalcin suppresses sulforaphane-induced apoptotic cell death which is partly mediated through caspase-3..
Int J Mol Med 2005 May
PMID:Overexpression of regucalcin suppresses apoptotic cell death in the cloned rat hepatoma H4-II-E cells induced by a naturally occurring isothiocyanate sulforaphane. 1580 9

The role of regucalcin, which is a regulatory protein in intracellular signaling pathway, in the regulation of cell proliferation was investigated by using the cloned normal rat kidney proximal tubular epithelial NRK52E cells over-expressing regucalcin. NRK52E cells were transfected with regucalcin (RC) pCXN2 vector and the multiple neomycin-resistant clones that stably overexpress regucalcin were selected. The regucalcin content of RC/pCXN2-transfected cells used in this study was about 21-fold as compared with that of the parental wild-type NRK52E cells. Wild-type NRK52E cells, pCXN2 vector-transfected cells (mock-type), and RC/pCXN2-transfected cells (transfectants) were cultured for 24, 48, and 72 h in the presence of bovine serum (5%). The cell numbers of wild- and mock-type were significantly increased with the time course of the culture. Cell numbers of transfectants were significantly suppressed as compared with that of wild- and mock-type. The decrease in cell number of wild-type cultured for 72 h in the presence of butyrate (8.3 x 10(-6) or 8.3 x 10(-5) M), rescovitine (10(-8) or 10(-7) M), or sulforaphane (10(-9) M), which is an inhibitor of the cell cycle, was not observed in transfectants. The effect of PD98059 (10(-8) M), staurosporine (10(-10) M) or dibucaine (10(-8)-10(-6) M), which is an inhibitor of protein kinases, in decreasing cell number of wild-type was not seen in transfectants. Moreover, the culture with wortmannin (10(-8) or 10(-7) M), an inhibitor of phosphatidylinositol 3 (PI3)-kinase, or Bay K 8644 (10(-8) or 10(-7) M), an agonist of calcium entry in cells, caused a significant decrease in cell number of the wild-type. This decrease was not observed in transfectants. The result of reverse transcription-polymerase chain reaction (RT-PCR) analysis using specific primers showed that c-jun and chk2 mRNA levels were significantly decreased in transfectant. p53 mRNA level was significantly increased in transfectants. The expression of c-myc, c-fos, cdc2, p21, and G3PDH mRNAs in transfectants was not significantly changed. This study demonstrates that overexpression of regucalcin has a suppressive effect on cell proliferation, which is mediated through various signaling pathways, in the cloned normal rat kidney proximal tubular epithelial NRK52E cells.
Int J Mol Med 2005 Oct
PMID:Overexpression of regucalcin suppresses cell proliferation of cloned normal rat kidney proximal tubular epithelial NRK52E cells. 1614 98

A novel protein RGPR-p117 was discovered as a regucalcin gene promoter region-related protein that binds to the TTGGC motif. The role of RGPR-p117 in cell function is unknown. The nuclear localization of RGPR-p117 was investigated using cloned normal rat kidney proximal tubular epithelial NRK52E cells in vitro. RGPR-p117 mRNA was expressed in NRK52E cells, and its expression was stimulated by culture with parathyroid hormone (10(-7) M) or phorbol 12-myristate (10(-6) M). RGPR-p117 was found to localize in the cytoplasm and nucleus with immunocytochemical and Western blot analysis using HA-RGPR-p117/phCMV2-transfected NRK52E cells. Overexpression of HA-RGPR-p117 was found to have a significant stimulatory effect on regucalcin mRNA expression in NRK52E cells. This study demonstrates that RGPR-p117 is localized in the nucleus of kidney cells, and may be involved in gene expression.
Int J Mol Med 2005 Nov
PMID:Nuclear localization of a novel protein, RGPR-p117, in cloned normal rat kidney proximal tubular epithelial cells. 1621 Dec 48


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