Regucalcin, a calcium-binding protein with a role in male reproduction?

Laurentino, Sandra; Correia, Sara; Cavaco, José E.; Oliveira, Pedro F.; Sousa, Mário; Barros, Alberto; Socorro, Sílvia

doi:10.1093/molehr/gar075

Cited by 38 publications

(33 citation statements)

References 110 publications

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“…Indeed, we have found increased expression of RGN in the testis of human infertile patients with hypospermatogenesis (Ref. 45). Although the causes of idiopathic hypospermatogenesis may be diverse, accelerated apoptosis, rather than proliferative dysfunction, has been implicated in the decreased number of spermatogonia (Ref.…”

Section: Clinical Findings Of Deregulated Apoptosis In the Testis Of mentioning

confidence: 98%

Oestrogens as apoptosis regulators in mammalian testis: angels or devils?

Correia

Cardoso

Cavaco

et al. 2015

Expert Rev. Mol. Med.

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In the mammalian testis, spermatogenesis is a highly coordinated process of germ cell development, which ends with the release of 'mature' spermatozoa. The fine regulation of spermatogenesis is strictly dependent on sex steroid hormones, which orchestrate the cellular and molecular events underlying normal development of germ cells. Sex steroids actions also rely on the control of germ cell survival, and the programmed cell death by apoptosis has been indicated as a critical process in regulating the size and quality of the germ line. Recently, oestrogens have emerged as important regulators of germ cell fate. However, the beneficial or detrimental effects of oestrogens in spermatogenesis are controversial, with independent reports arguing for their role as cell survival factors or as apoptosis-inducers. The dual behaviour of oestrogens, shifting from 'angels to devils' is supported by the clinical findings of increased oestrogens levels in serum and intratesticular milieu of idiopathic infertile men. This review aims to discuss the available information concerning the role of oestrogens in the control of germ cell death and summarises the signalling mechanisms driven oestrogen-induced apoptosis. The present data represent a valuable basis for the clinical management of hyperoestrogenism-related infertility and provide a rationale for the use of oestrogen-target therapies in male infertility.

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Section: Clinical Findings Of Deregulated Apoptosis In the Testis Of mentioning

confidence: 98%

Oestrogens as apoptosis regulators in mammalian testis: angels or devils?

Correia

Cardoso

Cavaco

et al. 2015

Expert Rev. Mol. Med.

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“…Taking into account that RGN is an androgen-responsive gene [12,14,17], we have used the androgen-sensitive LNCaP and the non-neoplastic PNT1A cell lines to evaluate the responsiveness of RGN expression to Ca In accordance with the results of mRNA expression, a significant reduction on RGN protein levels after treatment with 5 and 10 mM …”

Section: Extracellular Calcium Exerts a Biphasic Effect On Regucalcinmentioning

confidence: 99%

Effect of extracellular calcium on regucalcin expression and cell viability in neoplastic and non-neoplastic human prostate cells

Vaz

Rodrigues

Socorro

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Extracellular calcium (Ca2+o) and its receptor, the Ca2+-sensing receptor (CaSR), play an important role in prostate physiology, and it has been shown that the deregulation of Ca2+ homeostasis and the overexpression of CaSR are involved in prostate cancer (PCa). Regucalcin (RGN), a Ca2+-binding protein that plays a relevant role in intracellular Ca2+ homeostasis, was identified as an under-expressed protein in human PCa. Moreover, RGN was associated with suppression of cell proliferation, suggesting that the loss of RGN may favor development and progression of PCa. This work aims to unveil the role of Ca2+o on RGN expression and viability of non-neoplastic (PNT1A) and neoplastic (LNCaP) prostate cell lines. It was demonstrated that Ca2+o up-regulates RGN expression in both cell lines, but important differences were found between cells for dose- and time-responses to Ca2+o treatment. It was also shown that high [Ca2+]o triggers different effects on cell proliferation of neoplastic and non-neoplastic PCa cells, which seems to be related with RGN expression levels. This suggests the involvement of RGN in the regulation of cell proliferation in response to Ca2+o treatment. Also, the effect of Ca2+o on CaSR expression seems to be dependent of RGN expression, which is strengthened by the fact that RGN-knockdown in PNT1A cells increases the CaSR expression, whereas transgenic rats overexpressing RGN exhibit low levels of CaSR. Overall, our results highlighted the importance of RGN as a regulatory protein in Ca2+-dependent signaling pathways and its deregulation of RGN expression by Ca2+o may contribute for onset and progression of PCa.

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“…Regucalcin plays a multifunctional role in cell regulation; maintaining of intracellular calcium homeostasis in many cell types, suppressions of various signaling pathways from the cytoplasm to nucleus in proliferating cells, and regulation of nuclear functions including DNA and RNA synthesis [5, 14, 17–19]. Regucalcin has also been shown to suppress protein synthesis and activate proteases, suggesting an involvement in protein turnover in cells [20, 21].…”

Section: Introductionmentioning

confidence: 99%

The anti-apoptotic effect of regucalcin is mediated through multisignaling pathways

Yamaguchi

2013

Apoptosis

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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 Ca2+-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 Ca2+-activated DNA fragmentation, Ca2+/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.

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Regucalcin, a calcium-binding protein with a role in male reproduction?

Cited by 38 publications

References 110 publications

Oestrogens as apoptosis regulators in mammalian testis: angels or devils?

Oestrogens as apoptosis regulators in mammalian testis: angels or devils?

Effect of extracellular calcium on regucalcin expression and cell viability in neoplastic and non-neoplastic human prostate cells

The anti-apoptotic effect of regucalcin is mediated through multisignaling pathways

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