Role of regucalcin in liver nuclear function: Binding of regucalcin to nuclear protein or DNA and modulation of tumor-related gene expression

Tsurusaki, Yoshinori; Yamaguchi, Masayoshi

doi:10.3892/ijmm.14.2.277

Cited by 42 publications

(46 citation statements)

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“…We think that the use of different fixation protocols may be causing this histological artifact. RGN immunostaining is visible in cytoplasm as well as in nucleus, which is in accordance with reports showing that RGN is able to translocate to the nucleus regulating DNA synthesis and gene expression (Inagaki & Yamaguchi 2001, Tsurusaki & Yamaguchi 2004, Maia et al 2009). This is the first report describing RGN expression and localization in testis of any vertebrate.…”

Section: Discussionsupporting

confidence: 78%

Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis

Laurentino

Correia

Cavaco³

et al. 2011

Reproduction

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Regucalcin (RGN) is a calcium (Ca 2C )-binding protein which regulates intracellular Ca 2C homeostasis by modulating the activity of enzymes regulating Ca 2C concentration and enhancing Ca 2C -pumping activity. Several studies have described the pivotal role of proper Ca 2C homeostasis regulation to spermatogenesis and male fertility. Recently, RGN was identified as a sex steroid-regulated gene in prostate and breast; however, a possible role of RGN in spermatogenesis has not been examined. In this study, the expression and localization of RGN in rat and human testis, and other rat reproductive tissues was analyzed. Moreover, we studied whether RGN protein was present in seminiferous tubule fluid (STF). Finally, we examined the effect of 5a-dihydrotestosterone (DHT) on the expression of Rgn mRNA in rat seminiferous tubules (SeT) cultured ex vivo. The results presented in this study show that RGN is expressed in Leydig and Sertoli cells, as well as in all types of germ cells of both rat and human testis. RGN is also expressed in rat prostate, epididymis, and seminal vesicles. Moreover, RGN protein is present in rat STF. The results also demonstrate that Rgn expression is age dependent in rat testis, and is upregulated by the non-aromatizable androgen DHT in rat SeT cultured ex vivo. Taken together, these findings indicate that Rgn is a novel androgen-target gene in rat testis and that it may have a role in male reproductive function, particularly in the control of spermatogenesis.

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Section: Discussionsupporting

confidence: 78%

Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis

Laurentino

Correia

Cavaco³

et al. 2011

Reproduction

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“…Regucalcin binds to nuclear protein and DNA, and it modulates tumor-related gene expression in the liver cells [Tsurusaki and Yamaguchi, 2004]. Whether regucalcin can directly modulate gene expression in the nucleus of kidney cells is unknown.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of regucalcin suppresses apoptotic cell death in cloned normal rat kidney proximal tubular epithelial NRK52E cells: Change in apoptosis‐related gene expression

Nakagawa

Yamaguchi

2005

J of Cellular Biochemistry

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101

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The effect of regucalcin, a regulatory protein in intracellular signaling pathway, on cell death and apoptosis was investigated using the cloned normal rat kidney proximal tubular epithelial NRK52E cells overexpressing regucalcin. NRK52E cells (wild type) and stable regucalcin (RC)/pCXN2 transfectants were cultured for 72 h in a medium containing 5% bovine serum (BS) to obtain subconfluent monolayers. After culture for 72 h, cells were further cultured for 24-72 h in a medium without BS containing either vehicle, tumor necrosis factor-alpha (TNF-alpha; 0.1 or 1.0 ng/ml of medium), lipopolysaccharide (LPS; 0.1 or 1.0 microg/ml), Bay K 8644 (10(-9)-10(-7) M), or thapsigargin (10(-9)-10(-7) M). The number of wild-type cells was significantly decreased by culture for 42-72 h in the presence of TNF-alpha (0.1 or 1.0 ng/ml), LPS (0.1 or 1.0 microg/ml), Bay K 8644 (10(-7)-10(-5) M), or thapsigargin (10(-8) or 10(-7) M). The effect of TNF-alpha (0.1 or 1.0 ng/ml), LPS (0.1 or 1.0 microg/ml), Bay K 8644 (10(-7)-10(-6) M), or thapsigargin (10(-7) M) in decreasing the number of wild-type cells cultured for 24-72 h was significantly prevented in transfectants overexpressing regucalcin. Agarose gel electrophoresis showed the presence of low-molecular-weight deoxyribonucleic acid (DNA) fragments of adherent wild-type cells cultured with LPS (1.0 microg/ml), Bay K 8644 (10(-7) M), or thapsigargin (10(-8) M) for 24 h, and this DNA fragmentation was significantly suppressed in transfectants. DNA fragmentation in adherent cells was not seen by culture with TNF-alpha (1.0 ng/ml). TNF-alpha-induced decrease in the number of wild-type cells was significantly prevented by culture with caspase-3 inhibitor (10(-8) M), while LPS- or Bay K 8644-induced decrease in cell number was significantly prevented by caspase-3 inhibitor or N omega-nitro-L-arginine methylester (NAME) (10(-5) M), an inhibitor of nitric oxide (NO) synthase. Thapsigargin-induced decrease in cell number was not prevented in the presence of two inhibitors. Bcl-2 and Akt-1 mRNA levels were significantly increased in transfectants cultured for 24 h as compared with those of wild-type cells, while Apaf-1, caspase-3, or glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) mRNA expressions were not significantly changed in transfectants. Culture with TNF-alpha (1.0 ng/ml), LPS (1.0 microg/ml), Bay K 8644 (l0(-7) M), or thapsigargin (10(-8) M) caused a significant increase in caspase-3 mRNA levels in wild-type cells. LPS (1.0 microg/ml) significantly decreased Bcl-2 mRNA expression in the cells. Their effects on the gene expression of apoptosis-related proteins were not significantly changed in transfectants. This study demonstrates that overexpression of regucalcin has a suppressive effect on cell death and apoptosis induced by various factors which their action are mediated through many intracellular signaling pathways, and that it modulates the gene expression of apoptosis-related proteins.

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“…In addition, over-expression of SMP30 alters the expression of tumor-related genes such as c- myc , Ha- ras, c-src, p53, and Rb (retinoblastoma protein). In rat liver cells with over-expressing SMP30, the expression of the oncogenes c- myc, Ha- ras , and c-src was suppressed, while expression of the tumor suppressor genes p53 and Rb were up-regulated compared to wild type cells (79, 80). This suggests a protective role of SMP30 against cancer development.…”

Section: Smp30 and Cancermentioning

confidence: 96%

Senescence marker protein 30: functional and structural insights to its unknown physiological function

Scott

Bahnson

2011

BioMolecular Concepts

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Senescence marker protein 30 (SMP30) is a multifunctional protein involved in cellular Ca2+ homeostasis and the biosynthesis of ascorbate in non-primate mammals. The primary structure of the protein is highly conserved among vertebrates, suggesting the existence of a significant physiological function common to all mammals, including primates. Enzymatic activities of SMP30 include aldonolactone and organophosphate hydrolysis. Protective effects against apoptosis and oxidative stress have been reported. X-ray crystallography revealed that SMP30 is a six-bladed β-propeller with structural similarity to paraoxonase 1, another protein with lactonase and organophosphate hydrolase activities. SMP30 has recently been tied to several physiological conditions including osteoporosis, liver fibrosis, diabetes, and cancer. This review aims to describe the recent advances made toward understanding the connection between molecular structure, enzymatic activity and physiological function of this highly conserved, multifaceted protein.

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Role of regucalcin in liver nuclear function: Binding of regucalcin to nuclear protein or DNA and modulation of tumor-related gene expression

Cited by 42 publications

References 0 publications

Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis

Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis

Overexpression of regucalcin suppresses apoptotic cell death in cloned normal rat kidney proximal tubular epithelial NRK52E cells: Change in apoptosis‐related gene expression

Senescence marker protein 30: functional and structural insights to its unknown physiological function

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