CIRBP Ameliorates Neuronal Amyloid Toxicity via Antioxidative and Antiapoptotic Pathways in Primary Cortical Neurons

Abstract

It is generally accepted that the amyloid β (Aβ) peptide toxicity contributes to neuronal loss and is involved in the initiation and progression of Alzheimer’s disease (AD). Cold-inducible RNA-binding protein (CIRBP) is reported to be a general stress-response protein, which is induced by different stress conditions. Previous reports have shown the neuroprotective effects of CIRBP through the suppression of apoptosis via the Akt and ERK pathways. The objective of this study is to examine the effect of CIRBP against Aβ-induced toxicity in cultured rat primary cortical neurons and attempt to uncover its underlying mechanism. Here, MTT, LDH release, and TUNEL assays showed that CIRBP overexpression protected against both intracellular amyloid β- (iAβ-) induced and Aβ25-35-induced cytotoxicity in rat primary cortical neurons. Electrophysiological changes responsible for iAβ-induced neuronal toxicity, including an increase in neuronal resting membrane potentials and a decrease in K+ currents, were reversed by CIRBP overexpression. Western blot results further showed that Aβ25-35 treatment significantly increased the level of proapoptotic protein Bax, cleaved caspase-3, and cleaved caspase-9 and decreased the level of antiapoptotic factor Bcl-2, but were rescued by CIRBP overexpression. Furthermore, CIRBP overexpression prevented the elevation of ROS induced by Aβ25-35 treatment by decreasing the activities of oxidative biomarker and increasing the activities of key enzymes in antioxidant system. Taken together, our findings suggested that CIRBP exerted protective effects against neuronal amyloid toxicity via antioxidative and antiapoptotic pathways, which may provide a promising candidate for amyloid-based AD prevention or therapy.

The Construction of Bone Metastasis-Specific Prognostic Model and Co-expressed Network of Alternative Splicing in Breast Cancer

“…Until now, there is no evidence about the direct regulation between CIRBP and FAM110B. Furthermore, they are both involved in cell-cycle progression based on the up-to-date reports ( Hauge et al, 2007 ; Zhu et al, 2016 ; Su et al, 2020 ), and we found out that they are co-expressed in the BRCA database. To go through the mechanism of CIRBP regulating FAM110B-83922-ES, fatty acid metabolism was detected as the possible pathway connecting them.…”

“…CIRBP, cold-inducible RNA-binding protein, belonging to the cold-shock protein family, is expressed in different cell types and was involved in various cancer pathological processes, including cell survival, cell proliferation, and cancer ( Zhu et al, 2016 ; Su et al, 2020 ). It was reported that CIRBP had different effects in various cancers according to the cell context such as acting as a tumor suppressor in rectal carcinoma, endometrial carcinoma, and ovarian tumor and having pro-tumorigenic influences on melanoma, colorectal cancer, prostate cancer, central-nervous-system-related tumor, liver-pancreas carcinomas, skin squamous cell carcinoma, bladder cancer, and pituitary corticotrope adenoma ( Zhu et al, 2016 ; Liao et al, 2017 ; Zhong and Huang, 2017 ; Chen et al, 2018 ; Colasanti et al, 2018 ; Lujan et al, 2018 ; Lin et al, 2019 ).…”

MultiCens: Multilayer network centrality measures to uncover molecular mediators of tissue-tissue communication

“…In the AD network, irrespective of brain regions, genes JMJD6, SLC5A3, CIRBP, TARBP1 and AHSA1 are among the top ten central genes correlated with the SSG set, of which AHSA1 (activator of HSP90 ATPase activity 1) is already known to correlated with AD progression by promoting tau fibril formation [39]. On the other hand, CIRBP (cold inducible RNA binding protein) shields neurons from amyloid toxicity mediated by antioxidative and antiapoptotic pathways, making it a favourable molecule contending for AD prevention or therapy [40]. It may be worth studying the other three genes experimentally to test their connections to AD pathology.…”

Downregulation of CIRP Prone Cells to Oxidative Injury via Regulating Nrf2 Signaling Pathway

“…Once the Nrf2 signaling pathway is inhibited, excessive reactive oxygen species (ROS) will be produced, which is the main factor leading to apoptosis. A very recent study suggested a possible relationship between CIRP and Nrf2 signaling pathway [ 7 ]. For example, in the neurodegenerative amyloid toxicity cell model, overexpression of CIRP was shown to prevent the elevation of ROS and increase the activities of key enzymes in antioxidant system such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [ 7 ].…”

“…A very recent study suggested a possible relationship between CIRP and Nrf2 signaling pathway [ 7 ]. For example, in the neurodegenerative amyloid toxicity cell model, overexpression of CIRP was shown to prevent the elevation of ROS and increase the activities of key enzymes in antioxidant system such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [ 7 ]. Interestingly, all of these antioxidant genes are the downstream targets regulated by Nrf2 [ 8 ].…”