Effects of moderate and deep hypothermia on RNA-binding proteins RBM3 and CIRP expressions in murine hippocampal brain slices

Tong, Giang; Endersfelder, S.; Rosenthal, Lisa-Maria; Wollersheim, Sonja; Sauer, Igor M.; Bührer, Christoph; Berger, Felix; Schmitt, Katharina

doi:10.1016/j.brainres.2013.01.041

Cited by 73 publications

(66 citation statements)

References 23 publications

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“…Several studies have indicated that induction of CIRP expression by moderate hypothermia is associated with the protection of neural cell death from subsequent oxidative stresses [13,33,34]. Thus, intracellular CIRP has been implicated in responsible for hypothermia-induced neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia

Zhou

Yang

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Neuroinflammation is a key cascade after cerebral ischemia. Excessive production of proinflammatory mediators in ischemia exacerbates brain injury. Cold-inducible RNA- binding protein (CIRP) is a newly discovered proinflammatory mediator that can be released into the circulation during hemorrhage or septic shock. Here, we examine the involvement of CIRP in brain injury during ischemic stroke. Methods Stroke was induced by middle cerebral artery occlusion (MCAO). In vitro hypoxia was conducted in a hypoxia chamber containing 1% oxygen. CIRP and tumor necrosis factor-α (TNF-α) levels were assessed by RT-PCR and Western blot analysis. Results CIRP is elevated along with an upregulation of TNF-α expression in mouse brain after MCAO. In CIRP-deficient mice, the brain infarct volume, induction of TNF-α, and activation of microglia are markedly reduced after MCAO. Using microglial BV2 cells, we demonstrate that hypoxia induces the expression, translocation, and release of CIRP, which is associated with an increase of TNF-α levels. Addition of recombinant murine (rm) CIRP directly induces TNF-α release from BV2 cells and such induction is inhibited by neutralizing antisera to CIRP. Moreover, rmCIRP activates the NF-κB signaling pathway in BV2 cells. The conditioned medium from BV2 cells exposed to hypoxia triggers the apoptotic cascade by increasing caspase activity and decreasing Bcl-2 expression in neural SH-SY5Y cells, which is inhibited by antisera to CIRP. Conclusion Extracellular CIRP is a detrimental factor in stimulating inflammation to cause neuronal damage in cerebral ischemia. General significance Development of an anti-CIRP therapy may benefit patients with brain ischemia.

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Section: Discussionmentioning

confidence: 99%

Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia

Zhou

Yang

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…These CSPs have been identified in the mammalian brain [27–31] and CIRP was found in the brain and retina of a frog in the context of hybernation [32] but, to the best of our knowledge, they have not been localized in the mammalian retina. In this report, we identify the cold-induced responses of RBM3 and CIRP in cell lines of retinal origin as well as in retinas of neonatal and adult rats using quantitative real time PCR (qRT-PCR), Western blotting, and immunofluorescence.…”

Section: Introductionmentioning

confidence: 99%

Cold Shock Proteins Are Expressed in the Retina Following Exposure to Low Temperatures

et al. 2016

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Hypothermia has been proposed as a therapeutic intervention for some retinal conditions, including ischemic insults. Cold exposure elevates expression of cold-shock proteins (CSP), including RNA-binding motif protein 3 (RBM3) and cold inducible RNA-binding protein (CIRP), but their presence in mammalian retina is so far unknown. Here we show the effects of hypothermia on the expression of these CSPs in retina-derived cell lines and in the retina of newborn and adult rats. Two cell lines of retinal origin, R28 and mRPE, were exposed to 32°C for different time periods and CSP expression was measured by qRT-PCR and Western blotting. Neonatal and adult Sprague-Dawley rats were exposed to a cold environment (8°C) and expression of CSPs in their retinas was studied by Western blotting, multiple inmunofluorescence, and confocal microscopy. RBM3 expression was upregulated by cold in both R28 and mRPE cells in a time-dependent fashion. On the other hand, CIRP was upregulated in R28 cells but not in mRPE. In vivo, expression of CSPs was negligible in the retina of newborn and adult rats kept at room temperature (24°C). Exposure to a cold environment elicited a strong expression of both proteins, especially in retinal pigment epithelium cells, photoreceptors, bipolar, amacrine and horizontal cells, Müller cells, and ganglion cells. In conclusion, CSP expression rapidly rises in the mammalian retina following exposure to hypothermia in a cell type-specific pattern. This observation may be at the basis of the molecular mechanism by which hypothermia exerts its therapeutic effects in the retina.

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“…In contrast, RBM3 appears to be a potent neuroprotective protein. RBM3 mRNA/protein is increased in hippocampal slices by mild cooling to 33.5°C (Tong et al, 2013). Knockdown of RBM3 reduces hypothermia mediated neuroprotection in vitro (Chip et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons

et al. 2015

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Extremely mild hypothermia to 36.0°C is not thought to appreciably differ clinically from 37.0°C. However, it is possible that 36.0°C stimulates highly sensitive hypothermic signaling mechanism(s) and alters biochemistry. To the best of our knowledge, no such ultra-sensitive pathway/mechanisms have been described. Here we show that cold stress protein RNA Binding motif 3 (RBM3) increases in neuron and astrocyte cultures maintained at 33°C or 36°C for 24 or 48h, compared to 37°C controls. Neurons cultured at 36°C also had increased global protein synthesis (GPS). Finally, we found that melatonin or fibroblast growth factor 21 (FGF21) augmented RBM3 upregulation in young neurons cooled to 36°C. Our results show that a 1°C reduction in temperature can induce pleiotropic biochemical changes by upregulating GPS in neurons which may be mediated by RBM3 and that this process can be pharmacologically mimicked and enhanced with melatonin or FGF21.

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Effects of moderate and deep hypothermia on RNA-binding proteins RBM3 and CIRP expressions in murine hippocampal brain slices

Cited by 73 publications

References 23 publications

Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia

Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia

Cold Shock Proteins Are Expressed in the Retina Following Exposure to Low Temperatures

Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons

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