Differential Requirement for Nucleostemin in Embryonic Stem Cell and Neural Stem Cell Viability

Nomura, Jun; Maruyama, Masayoshi; Katano, Miyuki; Kato, Hidemasa; Zhang, Jiaxing; Masui, Shinji; Mizuno, Yosuke; Okazaki, Yasushi; Nishimoto, Masazumi; Okuda, Akihiko

doi:10.1002/stem.44

Cited by 29 publications

(34 citation statements)

References 49 publications

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“…However, in the current study, although caspase 3 was activated in response to NPR-C knockdown, the ES cells were maintained undifferentiated. In support to our results, a recent study has shown that loss of nucleostemin in ES cells leads to apoptosis with a dramatic increase in the levels of activated caspase 3 without affecting ES cell pluripotency [18]. Taken together, these findings suggest that loss of NPR-C may cause a low level of caspase 3 activation, which is not sufficient to induce differentiation.…”

Section: Npr-c Is Required For Es Cell Viabilitysupporting

confidence: 88%

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NPR-C Protects Embryonic Stem Cells from Apoptosis by Regulating p53 Levels

Abdelalim

Tooyama

2012

Stem Cells and Development

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The identification of intrinsic factors required for propagation of self-renewing embryonic stem (ES) cells is important to improve the efficiency of expansion of ES cells for therapeutic purposes. Here, we report a novel role for natriuretic peptide receptor-C (NPR-C) in the survival of murine ES cells. We found that NPR-C was highly expressed in ES cells and was downregulated during ES cell differentiation. Knockdown of NPR-C in ES cells by using a small-interfering RNA resulted in apoptotic cell death, and the induction of p53 protein expression. Conversely, chemical inhibition of p53 by α-pifithrin significantly reduced apoptosis in NPR-C-deficient cells. cANF((4-23)), a selective NPR-C agonist, protected ES cells against oxidative stress-induced apoptosis, and blocked activation of p53 and Nanog suppression in the presence of DNA-damaging agents. Thus, NPR-C is required to control DNA damage-induced p53 levels to maintain ES cell self-renewal.

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Section: Npr-c Is Required For Es Cell Viabilitysupporting

confidence: 88%

“…In ES cells, p53 is required to activate apoptosis [1,18]. We did not observe any increase in the levels of p53 mRNA ( Supplementary Fig.…”

Section: Npr-c Protects Es Cells From Apoptosis By Regulating P53mentioning

confidence: 44%

NPR-C Protects Embryonic Stem Cells from Apoptosis by Regulating p53 Levels

Abdelalim

Tooyama

2012

Stem Cells and Development

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“…However, the precise effects of NS vary among different cell lines. For example, loss of NS in embryonic stem cells results in loss of cell viability over long-term culture, whereas the viability of NS null neural stem/progenitor cells can be sustained for more than 10 passages without losing neural stem cell marker expression and bipotency (Nomura et al 2009). Silencing NS in PC3 cells results in increased numbers of apoptotic cells (Liu et al 2008), whereas apoptosis was not enhanced in NSmutant mouse embryos (Beekman et al 2006).…”

Section: Discussionmentioning

confidence: 97%

“…Previous studies about NS established the connection between NS and apoptosis populations (Nomura et al 2009). NS is concomitant with cellular proliferation and apoptosis, thus it is not surprising that NS-p53 pathway is activated in response to I/R and H/R.…”

Section: Discussionmentioning

confidence: 99%

Nucleostemin exerts anti-apoptotic function via p53 signaling pathway in cardiomyocytes

Zhang

Shi

Qian

et al. 2015

In Vitro Cell.Dev.Biol.-Animal

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Cardiomyocytes apoptosis following reperfusion injury causes irreversible damage to cardiac function. Understanding the mechanisms underlying cardiomyocytes death under these conditions can be helpful to identify strategies to abrogate such detrimental effects. Stem cell-specific proteins and regulatory pathways become important in understanding reparative processes in the myocardium. One such regulatory protein named nucleostemin (NS) has vital roles in cardiac ischemia. Although the relationship between NS and cell apoptosis has been studied, it is unknown how NS is controlled and how it participates in cardiomyocytes apoptosis induced by ischemia reperfusion (I/R). In the present study, we aimed to investigate the direct role of NS in myocardial I/R. In vivo, NS was highly expressed in cardiac tissues after I/R. Double immunofluorescent staining showed that NS located in the nucleolar of cardiomyocytes and correlated with cardiomyocytes apoptosis. Furthermore, in vitro primary rat cardiomyocytes increased NS expression induced by hypoxia-reoxygenation (H/R) treatment, in line with results in vivo. Suppression of NS expression by siNS promoted the expression of terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL)-positive cells p53 and cleaved caspase-3, which demonstrates I/R may require increased expression of NS to suppress p53 activation and maintain cardiomyocytes survival.

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“…NS possesses two putative GTP-binding motifs, and has been proposed as a marker for an undifferentiated or dedifferentiating state and for TICs in highly aggressive brain tumors (Kafienah et al, 2006;Tamase et al, 2009). The level of NS decreases drastically prior to cell cycle exit upon differentiation of the stem cells, suggesting that this protein may be an imperative protein for regulating the proliferation of stem cells and cancer cells, and in maintenance of their undifferentiated features (Jafarnejad et al, 2008;Nomura et al, 2009;Gao et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

In vitro Study of Nucleostemin as a Potential Therapeutic Target in Human Breast Carcinoma SKBR-3 Cells

Guo

Liao²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Although nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis and expression has been observed in some types of human cancer and stem cells, the molecular mechanisms involved in mediation of cell proliferation and cell cycling remains largely elusive. The aim of the present study was to evaluate NS as a potential target for gene therapy of human breast carcinoma by investigating NS gene expression and its effects on SKBR-3 cell proliferation and apoptosis. NS mRNA and protein were both found to be highly expressed in all detected cancer cell lines. The apoptotic rate of the pcDNA3.1-NS-Silencer group (12.1-15.4±3.8%) was significantly higher than those of pcDNA3.1-NS (7.2-12.0±1.7%) and non-transfection groups (4.1-6.5±1.8%, P<0.01). MTT assays showed the knockdown of NS expression reduced the proliferation rate of SKBR-3 cells significantly. Matrigel invasion and wound healing assays indicated that the number of invading cells was significantly decreased in the pcDNA3.1-NS-siRNA group (P<0.01), but there were no significant difference between non-transfected and over-expression groups (P>0.05). Moreover, RNAi-mediated NS downregulation induced SKBR-3 cell G1 phase arrest, inhibited cell proliferation, and promoted p53 pathway-mediated cell apoptosis in SKBR-3 cells. NS might thus be an important regulator in the G2/M check point of cell cycle, blocking SKBR-3 cell progression through the G1/S phase. On the whole, these results suggest NS might be a tumor suppressor and important therapeutic target in human cancers.

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Differential Requirement for Nucleostemin in Embryonic Stem Cell and Neural Stem Cell Viability

Cited by 29 publications

References 49 publications

NPR-C Protects Embryonic Stem Cells from Apoptosis by Regulating p53 Levels

NPR-C Protects Embryonic Stem Cells from Apoptosis by Regulating p53 Levels

Nucleostemin exerts anti-apoptotic function via p53 signaling pathway in cardiomyocytes

In vitro Study of Nucleostemin as a Potential Therapeutic Target in Human Breast Carcinoma SKBR-3 Cells

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