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 endogenous regucalcin in the regulation of protein tyrosine phosphatase activity in the proliferation of the cloned rat H4-II-E hepatoma cells was investigated. Cells were cultured for 6 to 96 h in a medium containing 1.0 or 10% fetal bovine serum (FBS). Cell numbers were significantly raised by culture with 10% FBS in comparison with that of 1.0% FBS. Protein tyrosine phosphatase activity in the cells was significantly elevated by culture with 10% FBS for 24 to 96 h as compared with that of 1% FBS. Such an increase was not seen in protein phosphatase activity toward phosphoserine or phosphothreonine. The presence of anti-regucalcin monoclonal antibody (50 or 100 ng/ml) in the enzyme reaction mixture caused a remarkable elevation of protein tyrosine phosphatase activity in the cells obtained by culture with 1.0 or 10% FBS. This elevation was completely prevented by the addition of regucalcin (10-6 M). The effect of antibody in elevating protein tyrosine phosphatase activity in the cells was significantly inhibited by the addition of okadaic acid (10-6 M) or vanadate (10(-6) M), an inhibitor of protein phosphatase, in the reaction mixture. The present study suggests that protein tyrosine phosphatase activity in the cloned rat hepatoma cells is increased in serum-stimulated cell proliferation, and that endogenous regucalcin has a suppressive role in the enhancement of the enzyme activity in proliferative cells.
Int J Mol Med 2000 Sep
PMID:Enhancement of protein tyrosine phosphatase activity in the proliferation of cloned rat hepatoma H4-II-E cells: suppressive role of endogenous regucalcin. 1093 98

The translocation of regucalcin to the nuclei of normal rat liver was investigated. The existence of endogenous regucalcin in isolated liver nuclei was confirmed by Western blotting using anti-regucalcin antibody. Nuclear translocation of regucalcin was estimated by sodium sulfate-polyacrylamide gel electrophoresis analysis. When isolated liver nuclei were incubated in the presence of exogenous regucalcin (50 microg/ml; 1.5 microM), potent band for regucalcin was found in the nuclei, indicating that the protein is translocated into the nucleus. This translocation was an early event. Nuclear regucalcin translocation was not appreciably changed in the presence of adenosine 5'-triphosphate (2 mM), guanosine 5'-triphosphate (2 mM), calcium chloride (0.1 mM), and the lectin wheat germ agglutinin (50 or 100 microg/ml), suggesting that its translocation is not mediated through nuclear localization signal. Moreover, Ca2+-dependent protein kinase and protein tyrosine phosphatase activities in isolated liver nuclei were significantly increased in the presence of anti-regucalcin monoclonal antibody (100 ng/ml) in the enzyme reaction mixture, and these increases were completely abolished by the addition of regucalcin (50 microg/ml). This study demonstrates that regucalcin is translocated into liver nucleus, and that it can regulate the nuclear function.
Int J Mol Med 2000 Dec
PMID:Translocation of regucalcin to rat liver nucleus: involvement of nuclear protein kinase and protein phosphatase regulation. 1107 24

Regucalcin, a regulatory protein of Ca2+ signaling, is mainly present in liver cells. The role of regucalcin in hepatoma cells, however, has not been clarified. The role of endogenous regucalcin in the regulation of protein tyrosine phosphatase activity in the cloned rat hepatoma cells (H4-II-E) was investigated. Hepatoma cells were cultured for 3 days in a medium containing serum (10% fetal bovine serum). After subconfluency, the cells were used for the assay of protein phosphatase activity toward phosphotyrosine. The expression of regucalcin in hepatoma cells was detected by Western blotting using anti-regucalcin antibody. Protein tyrosine phosphatase activity was exhibited in the cytosol of hepatoma cells. The enzyme activity in the cytosol of hepatoma cells was significantly elevated by the addition of calcium chloride (10(-6)-10(-4) M) in the reaction mixture. This elevation was completely blocked by the addition of trifluoperazine (TFP: 2.5 x 10(-6) M), an antagonist of calmodulin. The addition of regucalcin (10(-7) M) caused a complete inhibition of the calcium (10(-4) M)-increased enzyme activity. The presence of anti-regucalcin monoclonal antibody (25, 50, and 100 ng/ml) in the enzyme reaction mixture produced a significant increase in protein tyrosine phosphatase activity in the cytosols of hepatoma cells and normal liver cells. This increase was completely prevented by regucalcin addition. The effect of antibody (50 ng/ml) in elevating the enzyme activity was partly inhibited by vanadate (10(-4) M). Protein tyrosine phosphatase activity was significantly elevated by the culture with Bay K 8644, a Ca2+-channel agonist. This increase was blocked by TFP addition in the enzyme reaction mixture, and it was enhanced in the presence of anti-regucalcin antibody. The present study demonstrates that regucalcin is expressed in hepatoma cells (H4-II-E), and that the protein may have an inhibitory effect on Ca2+/calmodulin-dependent protein tyrosine phosphatase activity in the cells.
Mol Cell Biochem 2000 Oct
PMID:Role of endogenous regucalcin in protein tyrosine phosphatase regulation in the cloned rat hepatoma cells (H4-II-E). 1112 57

The alteration in Ca(2+)-ATPase activity in the brain plasma membrane of rats with increasing age was investigated. Calcium content in the brain tissues was significantly raised in aged rats (50 weeks old) as compared with that of young rats (5 weeks old). Increasing age caused a significant decrease in Ca(2+)-ATPase activity in the brain plasma membranes. The presence of N-ethylmaleimide (2.5 or 5 mM), a modifying reagent of thiol (SH)-groups, in the reaction mixture caused a significant decrease in the brain plasma membrane Ca(2+)-ATPase activity of young and aged rats, while dithiothreitol (2.5 or 5 mM), a protecting reagent of SH-groups, produced a significant increase in the enzyme activity, indicating that the SH-group is an active site of Ca(2+)-ATPase. The active site of Ca(2+)-ATPase may not be impaired by ageing. The brain plasma membrane Ca(2+)-ATPase activity of young rats was significantly reduced in the presence of dibutyryl cyclic AMP (10(-7)-10(-5) M) or inositol 1, 4, 5-trisphosphate (10(-7)-10(-5) M) in the reaction mixture. Such an decrease was not seen in aged rats. The responsibility for signaling factors seemed to be weakened by ageing. Calmodulin (2.5 and 5 microg/ml) or regucalcin (10(-8) and 10(-7) M), a Ca(2+)-regulating protein, did not have an effect on Ca(2+)-ATPase activity. This study demonstrates that ageing induces a decrease in Ca(2+)-ATPase activity in the brain plasma membranes. This finding suggests a cellular mechanism by which ageing causes calcium accumulation in brain.
Int J Mol Med 2001 Apr
PMID:Decrease in Ca2+-ATPase activity in the brain plasma membrane of rats with increasing age: involvement of brain calcium accumulation. 1125 83

The binding of nuclear factor on the promoter region of the regucalcin gene and the expression of regucalcin in the kidney cortex of rats was investigated. Nuclear extracts from kidney cortex were used for oligonucleotide competition gel mobility shift assay. An oligonucleotide between position -523 and -506 in the 5'-flanking region of the rat regucalcin gene, which contains a nuclear factor 1 (NF1) consensus motif TTGGC(N)6CC, competed with the probe for the binding of the nuclear protein from kidney cortex. The mutation of TTGGC in the consensus sequence caused an inhibition of the binding of nuclear factors. The binding of nuclear factor on the 5'-flanking region was clearly reduced in the kidney cortex obtained at 1, 2, and 3 days after a single intraperitoneal administration of cisplatin (1.0 mg/100 g body wt) to rats. Moreover, cisplatin administration caused a remarkable decrease in regucalcin mRNA levels and regucalcin concentration in the kidney cortex. Also, serum regucalcin concentration was significantly decreased by cisplatin administration. Meanwhile, serum urea nitrogen concentration was markedly elevated by cisplatin administration. The present study demonstrates that the specific nuclear factor binds to the NF1-like sequence in the promotor region of regucalcin gene in the kidney cortex of rats, and that the nuclear factor binding and regucalcin expression are suppressed by cisplatin administration.
Mol Cell Biochem 2001 Mar
PMID:Involvement of nuclear factor-1 (NF1) binding motif in the regucalcin gene expression of rat kidney cortex: the expression is suppressed by cisplatin administration. 1135 50

The molecular cloning and sequencing of the cDNA coding for a novel regucalcin gene promoter region-related protein (RGPR) was investigated using rat, mouse and human liver cDNA library with a yeast one-hybrid system and a rapid amplification of cDNA ends (RACE) method. The clone coding an unknown protein was isolated, and a novel protein was identified. This protein was termed as RGPR-p117. RGPR-p117 in rat, mouse and human liver consisted of 1058, 1051 and 1060 amino acid residues with calculated molecular mass of 117, 115 and 117 kDa and estimated pI of 5.69, 5.70 and 5.71, respectively. The homologies of amino acids among rat, mouse and human RGPR-p117 were at least 70%. RGPR-p117 had a leucine zipper motif. The expression of RGPR-p117 mRNA was found in the liver, kidney, heart, spleen, and brain of rats. The database search of the human RGPR-p117 showed that its gene consisted of at least 26 exons spanning approximately 4.1 kbp and localized on human chromosome 1q25.2. Furthermore, we found a cDNA clone which was highly identical to a front half part of the human RGPR-p117 cDNA, using the BLAST search of human RGPR-p117. This cDNA clone was a splicing variant of human RGPR-p117, which derived from human placental choriocarcinoma. Our study demonstrates that a novel gene coding RGPR-p117 is present in rat, mouse and human.
Int J Mol Med 2001 Nov
PMID:Molecular cloning and sequencing of the cDNA coding for a novel regucalcin gene promoter region-related protein in rat, mouse and human liver. 1160 20

The effect of regucalcin, a regulatory protein of Ca2+ signaling, on guanosine-5'-triphosphatase (GTPase) activity in isolated rat liver plasma membranes was investigated. GTPase activity was significantly increased by the addition of Ca2+ (25-100 microM) in the enzyme reaction mixture. Such an increase was not seen by other metals (Mg, Co, Zn, Cu, Ni and Mn) with 50 microM. The activatory effect of calcium (50 microM) was significantly decreased by calmodulin (2.5 and 5 microg/ml), indicating that it does not depend on calmodulin. The presence of regucalcin (0.1-0.5 microM) in the enzyme reaction mixture caused a significant increase in GTPase activity. This increase was not significantly enhanced by calcium (50 microM). GTPase activity was significantly increased by dithiothreitol (DTT; 5 mM), a protecting reagent of thiol (SH)-groups, while it was decreased by N-ethylmaleimide (NEM; 5 mM), a modifying reagent of SH-groups. The effect of calcium or regucalcin in increasing GTPase activity was not seen in the presence of NEM. Also, the activatory effect of calcium or regucalcin on GTPase was not seen in the presence of vanadate, an inhibitor of protein phosphorylation, which could inhibit GTPase activity. Moreover, the effect of regucalcin was not seen in the presence of digitonin (0.01%), a solubilizing reagent of membranous lipids, while the effect of calcium was not inhibited by digitonin. The present study demonstrates that regucalcin has an activatory effect on GTPase activity independently of Ca2+ in rat liver plasma membranes.
Mol Cell Biochem 2001 Aug
PMID:Activatory effect of regucalcin on GTPase activity in rat liver plasma membranes. 1169 88

The effect of regucalcin, a regulatory protein of Ca2+ signaling, on deoxyribonucleic acid (DNA) synthesis activity in the nuclei isolated from rat renal cortex was investigated. The addition of calcium chloride (10-100 microM) in the reaction mixture containing the nuclei caused a significant decrease in DNA synthesis activity. Nuclear DNA synthesis activity was significantly raised in the presence of EGTA (1 mM), a chelator of Ca2+, indicating that nuclear Ca2+ has an inhibitory effect. Regucalcin (0.1-0.5 microM) added in the reaction mixture in the presence of either EGTA (1 mM) or calcium chloride (50 microM) had a significant inhibitory effect on nuclear DNA synthesis activity. The presence of anti-regucalcin monoclonal antibody (10-50 ng/ml) in the reaction mixture caused a significant increase in DNA synthesis activity. This increase was completely abolished by the addition of regucalcin (0.5 microM). The effect of anti-regucalcin monoclonal antibody in increasing DNA synthesis was enhanced in the presence of EGTA. Additionally, an inhibitory effect of calcium chloride (10 or 50 microM) was enhanced in the presence of anti-regucalcin monoclonal antibody (25 ng/ml). The present study demonstrates that endogenous regucalcin has a suppressive effect on DNA synthesis in the nuclei of rat renal cortex.
Mol Cell Biochem 2002 Jan
PMID:Suppressive effect of endogenous regucalcin on deoxyribonuclic acid synthesis in the nuclei of rat renal cortex. 1193 41

The role of endogenous regucalcin in the regulation of bone metabolism was investigated by using regucalcin transgenic (TG) rats. The expression of regucalcin mRNA in the femoral-diaphyseal and -metaphyseal tissues of normal (wild-type) rats was shown by using reverse transcription-polymerase chain reaction (RT-PCR) with a specific primer of regucalcin cDNA. Regucalcin protein was detected in the femoral-diaphyseal and -metaphyseal tissues of normal (wild-type) rats using Western analysis. Regucalcin levels were significantly increased in the femoral-metaphyseal tissues of regucalcin TG male rats and in the diaphyseal and metaphyseal tissues of the TG female rats. The morphologic change in the femoral-diaphyseal and -metaphyseal tissues of regucalcin TG rats was demonstrated by using a peripheral quantitative computed tomography (pQCT); morphologic change was great in the femoral tissues of female rats as compared with that of male rats. Mineral content, mineral density and polar strength strain index in the femoral-diaphyseal and -metaphyseal tissues were markedly reduced in regucalcin TG female rats. A significant decrease in cortical thickness was seen in the femoral diaphysis of regucalcin TG female rats. Calcium content in the femoral-diaphyseal and -metaphyseal tissues was significantly decreased in regucalcin TG male and female rats; a remarkable decrease was seen in female rats. Femoral-metaphyseal alkaline phosphatase activity was significantly lowered in regucalcin TG female rats. The enzyme activity was not significantly changed in the femoral-diaphyseal tissues of the TG female rats. In the diaphyseal tissue of male rats, the enzyme activity was significantly decreased in the TG rats. A significant decrease in deoxyribonucleic acid (DNA) content was seen in the metaphyseal tissue of regucalcin TG male rats and in the diaphyseal and metaphyseal tissues of the TG female rats. This study demonstrates that bone loss is induced in the femoral tissue of regucalcin transgenic rats, and that a remarkable decrease in bone morphologic index and biochemical component was seen in the female rats. Regucalcin may be involved in the regulation of bone metabolism.
Int J Mol Med 2002 Oct
PMID:Role of endogenous regucalcin in bone metabolism: bone loss is induced in regucalcin transgenic rats. 1223 82

The role of regucalcin, a regulatory protein of Ca2+ signaling, in the regulation of nitric oxide (NO) synthase activity in the cytosol of rat heart muscle was investigated. The addition of calcium chloride (5-20 microM) into the enzyme reaction mixture containing the heart cytosolic protein caused a significant increase in NO synthase activity. The Ca2+ effect was significantly inhibited by trifluoperazine (TFP; 20 or 50 microM), an antagonist of calmodulin, indicating the existence of Ca2+/calmodulin-dependent NO synthase activity in rat heart muscle cytosol. NO synthase activity was significantly decreased by the addition of regucalcin (10(-9) or 10(-8) M). This effect was also seen in the presence of calcium chloride (10 microM), TFP (50 microM) or EGTA (1 mM), a chelator of Ca2+. Meanwhile, the effect of regucalcin (10(-8) M) in decreasing NO synthase activity was not seen in the presence of Nw-nitro-L-arginine methylester (NAME; 10(-6) or 10(-5) M), an inhibitor of the enzyme. The presence of anti-regucalcin monoclonal antibody (25 or 50 ng/ml) in the enzyme reaction mixture caused a significant increase in NO synthase activity. This effect was completely abolished by the addition of regucalcin (10(-7) M). NO synthase activity was not significantly changed in the heart muscle cytosol of transgenic rats overexpressing endogenous regucalcin as compared with that of wild-type rats. However, the effect of calcium (10 micro M) addition in increasing NO synthase activity was significantly weakened in the heart muscle cytosol of regucalcin transgenic rats. The present study demonstrates that endogenous regucalcin has a suppressive effect on NO synthase activity in the heart muscle cytosol of rats.
Int J Mol Med 2002 Dec
PMID:Suppressive role of endogenous regucalcin in the regulation of nitric oxide synthase activity in heart muscle cytosol of normal and regucalcin transgenic rats. 1243 4


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