Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein. Brain Res
ABSTRACT We hypothesized that one of the mechanisms underlying the protection of brain injury by therapeutic hypothermia is associated with preservation of neural stem cells. We investigated effects of moderate low temperature and the contribution of a cold-inducible molecule for the stemness of neural stem cells. The MEB5 mouse neural stem cell line was cultured in the presence or absence of EGF, and apoptosis, mRNA expression, and immunocytochemistry of the differentiation markers nestin and GFAP were evaluated at 37 or 32°C. We investigated the contribution of the cold-inducible RNA binding protein (CIRP) on apoptosis and differentiation of MEB5 cells at 32°C. EGF deprivation increased the number of apoptotic cells, decreased expression of nestin, and increased expression of GFAP. The moderate low temperature prevented apoptosis and decreases in expression of GFAP in MEB5 by EGF deprivation. The moderate low temperature significantly increased expression of CIRP. siRNA against CIRP significantly increased the apoptotic cell population of MEB5 cells via EGF deprivation at 32°C. These findings suggest that moderate low temperature preserved stemness of neural stem cells and prevented cell apoptosis via the stimulation of CIRP, and one of the mechanisms of rescue of brain injury by the moderate hypothermia is associated with preservation of neural stem cells.
- SourceAvailable from: Ho Hee Jang
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- "Moderate low temperature prevents epidermal growth factor (EGF) deprivation-induced apoptosis through upregulation of CIRP expression in neural stem cells . In addition, overexpressing CIRP protects cells from TNF-a-induced apoptosis by activating extracellular signal-regulated kinase (ERK) pathways in CIRPdeficient mouse fibroblasts . "
ABSTRACT: CIRP has been implicated in apoptosis, yet its mechanism of action remains unknown. To determine the role of CIRP in DNA damage-induced apoptosis, we performed CIRP overexpression and knockdown experiments to investigate the effects of CIRP on key molecules in apoptosis pathway. Etoposide treatment was used to induce DNA damage-induced apoptosis. We found that CIRP knockdown increased p53 level, which in turn up-regulated pro-apoptotic genes and down-regulated anti-apoptotic genes. In contrast, CIRP overexpression decreased p53 level, which in turn down-regulated pro-apoptotic genes and up-regulated anti-apoptotic genes. The change in the expression levels of pro-apoptotic and anti-apoptotic genes shifts the balance between life and death of cells. CIRP expression is upregulated by chronic inflammation, and this phenomenon provides an interesting interventional opportunity in cancers arising from chronic inflammation. Chronic inflammation up-regulates CIRP, which in turn inhibit apoptosis. Therefore, inhibiting the function of up-regulated CIRP may have a therapeutic value in cancer. Copyright © 2015. Published by Elsevier Inc.Biochemical and Biophysical Research Communications 07/2015; DOI:10.1016/j.bbrc.2015.07.066 · 2.28 Impact Factor
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- "Using cultured neural stem cells, Saito and co-workers  reported an increase in mRNA expression for CIRBP and the protein abundance at 32°C compared to those cultured at 37°C. In addition, the knockdown of this gene by RNA interference in neural stem cells showed an increase in apoptotic cell population, indicating the cytoprotective effect of this protein . The up-regulation of cirbp mRNA was also reported when salmon was subjected to hyperosmotic stress during the transition from freshwater to marine environment . "
ABSTRACT: The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the brain of P. annectens during the induction (6 days) and maintenance (6 months) phases of aestivation as compared with the freshwater control using suppression subtractive hybridization. During the induction phase of aestivation, the mRNA expression of prolactin (prl) and growth hormone were up-regulated in the brain of P. annectens, which indicate for the first time the possible induction role of these two hormones in aestivation. Also, the up-regulation of mRNA expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein γ polypeptide and the down-regulation of phosphatidylethanolamine binding protein, suggest that there could be a reduction in biological and neuronal activities in the brain. The mRNA expression of cold inducible RNA-binding protein and glucose regulated protein 58 were also up-regulated in the brain, probably to enhance their cytoprotective effects. Furthermore, the down-regulation of prothymosin α expression suggests that there could be a suppression of transcription and cell proliferation in preparation for the maintenance phase. In general, the induction phase appeared to be characterized by reduction in glycolytic capacity and metabolic activity, suppression of protein synthesis and degradation, and an increase in defense against ammonia toxicity. In contrast, there was a down-regulation in the mRNA expression of prl in the brain of P. annectens during the maintenance phase of aestivation. In addition, there could be an increase in oxidative defense capacity, and up-regulation of transcription, translation, and glycolytic capacities in preparation for arousal. Overall, our results signify the importance of reconstruction of protein structures and regulation of energy expenditure during the induction phase, and the needs to suppress protein degradation and conserve metabolic fuel stores during the maintenance phase of aestivation.PLoS ONE 08/2013; 8(8):e71205. DOI:10.1371/journal.pone.0071205 · 3.23 Impact Factor
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- "The GO enrichment analyses showed that the genes which were upregulated upon Cirbp or Rbm3 depletion were significantly enriched in cell cycle (Supplementary Table S7). This result was consistent with the previous studies that Cirbp and Rbm3 regulated cellular proliferation40414243. To assess the influence of Cirbp or Rbm3 on the stability of their target transcripts, we compared the mRNA levels from knockdown and mock cells. "
ABSTRACT: The body temperature is considered a universal cue by which the master clock synchronizes the peripheral clocks in mammals, but the mechanism is not fully understood. Here we identified two cold-induced RNA-binding proteins (RBPs), Cirbp and Rbm3, as important regulators for the temperature entrained circadian gene expression. The depletion of Cirbp or Rbm3 significantly reduced the amplitudes of core circadian genes. PAR-CLIP analyses showed that the 3'UTR binding sites of Cirbp and Rbm3 were significantly enriched near the polyadenylation sites (PASs). Furthermore, the depletion of Cirbp or Rbm3 shortened 3'UTR, whereas low temperature (upregulating Cirbp and Rbm3) lengthened 3'UTR. Remarkably, we found that they repressed the usage of proximal PASs by binding to the common 3'UTR, and many cases of proximal/distal PAS selection regulated by them showed strong circadian oscillations. Our results suggested that Cirbp and Rbm3 regulated the circadian gene expression by controlling alternative polyadenylation (APA).Scientific Reports 06/2013; 3:2054. DOI:10.1038/srep02054 · 5.58 Impact Factor