HSP90β is involved in signaling prolactin-induced apoptosis in newt testis

Saribek, Buget; Jin, Yuji; Saigo, Mikiko; Eto, Kojiro; Abe, Shinichi

doi:10.1016/j.bbrc.2006.08.143

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…Dissociated cells from testes were prepared as described (9). Healthy nuclei were isolated from the dissociated germ cells by solubilization for 5 min on ice with 40 ng/ml digitonin in nuclear isolation buffer (NB: 10 mM PIPES, pH 7.4, 10 mM KCl, 2 mM MgCl 2 ,1 mM DTT, 1 mM PMSF, protease inhibitor mixture, RNase inhibitor).…”

Section: Methodsmentioning

confidence: 99%

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Reduced Expression of an RNA-binding Protein by Prolactin Leads to Translational Silencing of Programmed Cell Death Protein 4 and Apoptosis in Newt Spermatogonia

Eto

Eda

Hayano

et al. 2009

Journal of Biological Chemistry

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Recent studies indicate that the balance between cell survival and proapoptotic signals determines which cells commit to life or death. We have shown that the balance between follicle-stimulating hormone and prolactin determines differentiation or apoptosis in 7th generation spermatogonia during newt spermatogenesis; however, the molecular mechanisms specifying their fate are poorly understood. Here we show that the newt RNA-binding protein (nRBP) plays a critical role in determining their fate. nRBP was identified as a clone whose mRNA is decreased by prolactin, resulting in the reduction of the protein, which is otherwise expressed predominantly in the spermatogonia. nRBP protein associated with the mRNA for newt programmed cell death protein 4 (nPdcd4) at the 3-untranslated region. nRBP reduction increased nPdcd4 mRNA but decreased its protein. In a cell-free system, cytoplasmic extracts containing reduced amounts of nRBP and nPdcd4 protein induced apoptosis, whereas adding nRBP protein to the extracts blocked apoptosis. Furthermore, overexpression of nRBP protected cells from apoptosis, stabilized the chimeric transcript containing the nPdcd4 3-untranslated region, and accelerated its translation. These data suggest that, in the absence of nRBP, nPdcd4 mRNA is not stabilized and its translation is suppressed, leading to apoptosis in the spermatogonia.Multicellular organisms maintain tissue homeostasis through response of their cells to extracellular signals that either promote their proliferation and differentiation or induce their death. Evidence is accumulating that extracellular stimuli, such as growth factors and cytokines, operate via complex signal transduction networks that ultimately control cellular fates (1); however, the complete molecular mechanisms need to be elucidated.One convenient system for studying the molecular mechanisms governing cell survival and death is spermatogenesis. It is mediated not only by cell proliferation and differentiation but also by programmed cell death or apoptosis, culminating in the production of spermatozoa. Apoptosis is necessary for eliminating unwanted cells and adjusting cell numbers in multicellular organisms to ensure tissue homeostasis.In the testis of the Japanese red-bellied newt, Cynops pyrrhogaster, primary spermatogonia proliferate through seven mitotic divisions, and then in the 8th generation the spermatogonia differentiate into primary spermatocytes and initiate meiosis in the spring when the ambient temperature is high; in contrast, in the autumn when the ambient temperature is low, the spermatogonia often undergo apoptosis in the 7th generation, resulting in the cessation of spermatogenesis (2). These findings suggest the existence of molecular mechanisms regulating the fate of 7th generation spermatogonia.We have shown in vitro and in vivo that the cellular fate in the spermatogonia is mainly regulated by changes in the endogenous levels of two peptide hormones secreted from the pituitary gland as follows: follicle-stimulating hormone (FSH) 2 th...

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Section: Methodsmentioning

confidence: 99%

“…*, p Ͻ 0.01. B, alignment of deduced amino acid sequence of nRBP with those of X. laevis (x) CIRP2 (12), xCIRP (11), axolotl (Ax) RNA-binding protein (9), mouse (m) CIRP (41), mRBM3 (8), human (h) CIRP (10), and hRBM3 (7). The amino acid numbers are at both sides of the sequences.…”

Section: Methodsmentioning

confidence: 99%

Reduced Expression of an RNA-binding Protein by Prolactin Leads to Translational Silencing of Programmed Cell Death Protein 4 and Apoptosis in Newt Spermatogonia

Eto

Eda

Hayano

et al. 2009

Journal of Biological Chemistry

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“…The role of prolactin as an early acute stress in adult ICU sepsis and trauma patients has not been elucidated yet [6]. In an animal model, a possible relationship between heat shock proteins (HSPs) and prolactin receptors has been previously reported [7]. …”

Section: Introductionmentioning

confidence: 99%

Early Response Roles for Prolactin Cortisol and Circulating and Cellular Levels of Heat Shock Proteins 72 and 90α in Severe Sepsis and SIRS

Vardas

Apostolou

Briassouli

et al. 2014

BioMed Research International

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Objective. To evaluate the early heat shock protein (HSP) and hormonal stress response of intensive care unit (ICU) patients with severe sepsis/septic shock (SS) or systemic inflammatory response syndrome (SIRS) compared to healthy subjects (H). Methods. Patients with early (first 48 hrs) SS (n = 29) or SIRS (n = 29) admitted to a university ICU and 16 H were enrolled in the study. Serum prolactin, cortisol, and plasma ACTH were determined using immunoassay analyzers. ELISA was used to evaluate extracellular HSPs (eHSP90α, eHSP72) and interleukins. Mean fluorescence intensity (MFI) values for intracellular HSPs (iHSP72, iHSP90α) were measured using 4-colour flow-cytometry. Results. Prolactin, cortisol, and eHSP90α levels were significantly increased in SS patients compared to SIRS and H (P < 0.003). ACTH and eHSP72 were significantly higher in SS and SIRS compared to H (P < 0.005). SS monocytes expressed lower iHSP72 MFI levels compared to H (P = 0.03). Prolactin was related with SAPS III and APACHE II scores and cortisol with eHSP90α, IL-6, and lactate (P < 0.05). In SS and SIRS eHSP90α was related with eHSP72, IL-6, and IL-10. Conclusion. Prolactin, apart from cortisol, may have a role in the acute stress response in severe sepsis. In this early-onset inflammatory process, cortisol relates to eHSP90α, monocytes suppress iHSP72, and plasma eHSP72 increases.

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“…Saribek et al reported that Hsp90β mediates the signaling of prolactin to trigger apoptosis (Saribek et al, 2006). Because prolactin has more than 300 biological effects reported, it is not clear if this was a primary or secondary effect.…”

Section: Hsp90α Versus Hsp90βmentioning

confidence: 99%

Extracellular Hsp90 (eHsp90) as the Actual Target in Clinical Trials

Li¹,

Tsen²,

Sahu³

et al. 2013

International Review of Cell and Molecular Biology

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Despite extensive investigative studies and clinical trials over the past two decades, we still do not understand why cancer cells are more sensitive to the cellular toxicity of Hsp90 inhibitors than normal cells. We still do not understand why only some cancer cells are sensitive to the Hsp90 inhibitors. Based on studies of the past few years, we argue that the selected sensitivity of cancer cells to Hsp90 inhibitors, such as 17-N-allylamino-17-demethoxygeldanamycin, is due to inhibition of the extracellular Hsp90 (eHsp90) rather than intracellular Hsp90 by these inhibitors. Because not all tumor cells utilize eHsp90 for motility, invasion and metastasis, only the group of “eHsp90-dependent” cancer cells is sensitive to Hsp90 inhibitors. If these notions prove to be true, pharmaceutical agents that selectively target eHsp90 should be more effective on tumor cells and less toxic on normal cells than current inhibitors that nondiscriminatively target both extracellular and intracellular Hsp90.

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HSP90β is involved in signaling prolactin-induced apoptosis in newt testis

Cited by 15 publications

References 36 publications

Reduced Expression of an RNA-binding Protein by Prolactin Leads to Translational Silencing of Programmed Cell Death Protein 4 and Apoptosis in Newt Spermatogonia

Reduced Expression of an RNA-binding Protein by Prolactin Leads to Translational Silencing of Programmed Cell Death Protein 4 and Apoptosis in Newt Spermatogonia

Early Response Roles for Prolactin Cortisol and Circulating and Cellular Levels of Heat Shock Proteins 72 and 90α in Severe Sepsis and SIRS

Extracellular Hsp90 (eHsp90) as the Actual Target in Clinical Trials

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