Sodium Butyrate Protects N2a Cells against A? Toxicity In Vitro.
Ontology highlight
ABSTRACT:
SUBMITTER: Sun J
PROVIDER: S-EPMC7180402 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Sodium Butyrate Protects N2a Cells against A<i>β</i> Toxicity In Vitro.
Sun Jingxuan J Yuan Boyu B Wu Yancheng Y Gong Yuhong Y Guo Wenjin W Fu Shoupeng S Luan Yongxin Y Wang Wei W
Mediators of inflammation 20200415
Alzheimer's disease (AD) is a common neurodegenerative disease. A<i>β</i> plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against A<i>β</i> toxicity and to uncover the underlying mechanisms. The results showed t ...[more]
Similar Datasets
Project description:Parkinson's disease (PD), a progressive neurodegenerative disorder, is associated with the destruction of dopamine neurons in the substantia nigra (SN) and the formation of Lewy bodies in basal ganglia. Risk factors for PD include aging, as well as environmental and genetic factors. Recent converging reports suggest a role for the gut microbiome and epigenetic factors in the onset and/or progression of PD. Of particular relevance and potential therapeutic targets in this regard are histone deacetylases (HDACs), enzymes that are involved in chromatin remodeling. Butyrate, a short-chain fatty acid (FA) produced in the gut and presumably acting via several G protein-coupled receptors (GPCRs) including FA3 receptors (FA3Rs), is a well-known HDAC inhibitor that plays an important role in maintaining homeostasis of the gut-brain axis. Recently, its significance in regulation of some critical brain functions and usefulness in neurodegenerative diseases such as PD has been suggested. In this study we sought to determine whether butyrate may have protective effects against salsolionl (SALS)-induced toxicity in SH-SY5Y cells. SALS, an endogenous product of aldehyde and dopamine condensation, may be selectively toxic to dopaminergic neurons. SH-SY5Y cells, derived from human neuroblastoma cells, are used as a model of these neurons. Exposure of SH-SY5Y cells for 24 h to 400 μM SALS resulted in approximately 60% cell death, which was concentration-dependently prevented by butyrate. The effects of butyrate in turn were significantly attenuated by beta-hydroxy butyrate (BHB), a selective FA3R antagonist. Moreover, a selective FA3R agonist (AR 420626) also provided protective effects against SALS, which was totally blocked by BHB. These findings provide further support that butyrate or an agonist of FA3R may be of therapeutic potential in PD.
| S-EPMC7484007 | biostudies-literature
Project description:Sodium butyrate (NaBu) is regarded as a potential reagent for cancer therapy. In this study, a specific breast cancer cell population that is resistant NaBu treatment was identified. These cells possess cancer stem cell characters, such as the capability of sphere formation in vitro and high tumor incident rate (85%) in mouse model. Forty percent of the NaBu resistant cells express the cancer stem cells marker, the CD133, whereas only 10% intact cells present the CD133 antigen. Furthermore, the endogenous expressing c-MET contributes to the survival of cancer stem cell population from the treatment of NaBu. The CD133+ group also presents a higher level of c-MET. A combination treatment of MET siRNA and NaBu efficiently prohibited the breast cancer progression, and the incident rate of the tumor decrease to 18%. This study may help to develop a new and alternative strategy for breast cancer therapy.
| S-EPMC3257283 | biostudies-literature
Project description:The effects and underlying mechanisms of butyrate and butyrate+niacin on apoptosis in sheep rumen epithelial cells were investigated. Cells were exposed to butyrate (0-140 mM) for 6 h. A low concentration (20 mM) of butyrate increased cell viability and promoted growth whereas high concentrations (40-140 mM) inhibited proliferation. Cells were then cocultured with 120 mM butyrate and niacin (0-100 mM) for 6 h. Niacin addition attenuated butyrate-induced cellular damage and promoted proliferation at 20-80 mM; 40 mM presented the optimal effect. Higher concentrations (100 mM) of niacin resulted in low cell viability. Subsequent experiments confirmed that 120 mM butyrate increased intracellular reactive oxygen species (ROS) production and reduced the intracellular total antioxidant capacity (T-AOC) versus the untreated control. Compared with 120 mM butyrate, cotreatment with 40 mM niacin significantly reduced the intracellular ROS content and increased the intracellular T-AOC. Flow cytometry analysis revealed that 120 mM butyrate increased the proportion of apoptotic cells by 17.8% versus the untreated control, and 120 mM butyrate+40 mM niacin treatment reduced the proportion of apoptotic cells by 28.6% and 39.4% versus the untreated control and butyrate treatment, respectively. Treatment with 120 mM butyrate increased caspase-9 and p53 mRNA levels and decreased the expression of Bcl-2 and Bax, and the Bcl-2/Bax ratio versus the untreated control. Treatment with 120 mM butyrate+40 mM niacin downregulated the expression of caspase-3 and p53 and increased the expression of Bcl-2 and Bax versus butyrate treatment alone but had no effect on the Bcl-2/Bax ratio. Thus, high concentrations of butyrate may induce rumen epithelial cell apoptosis by increasing oxidative stress and inducing caspase-9 and p53 expression. Cotreatment with niacin regulates apoptosis-related gene expression by reducing intracellular ROS production and DNA damage and downregulating caspase-3 and p53 expressions to protect rumen epithelial cells against butyrate-induced apoptosis.
| S-EPMC6815573 | biostudies-literature
Project description:Hexavalent chromium [Cr(VI)] is a human carcinogen that results in the generation of reactive oxygen species (ROS) and a variety of DNA lesions leading to cell death. Epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent antioxidative activity capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. Here we demonstrated that co-treatment with EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death in a dose-dependent manner. Cr(VI) induces apoptosis as the primary mode of cell death. Co-treatment of BEAS-2B cells with EGCG dose-dependently suppressed Cr(VI)-induced apoptosis. Fluorescence microscopic analyses and quantitative measurement revealed that EGCG significantly decreased intracellular levels of ROS induced by Cr(VI) exposure. Using a well-established K(+)/SDS precipitation assay, we further showed that EGCG was able to dose-dependently reduce DNA-protein cross-links (DPC), lesions that could be partially attributed to Cr(VI)-induced oxidative stress. Finally, analyses of Affymetrix microarray containing 28,869 well-annotated genes revealed that, among the 3412 genes changed more than 1.5-fold by Cr(VI) treatment, changes of 2404 genes (70%) were inhibited by pretreatment of EGCG. Real-time PCR confirmed the induction of 3 genes involved in cell death and apoptosis by Cr(VI), which was eliminated by EGCG. In contrast, Cr(VI) reduced the expression of 3 genes related to cellular defense, and this reduction was inhibited by EGCG. Our results indicate that EGCG protects BEAS-2B cells from Cr(VI)-induced cytotoxicity presumably by scavenging ROS and modulating a subset of genes. EGCG, therefore, might serve as a potential chemopreventive agent against Cr(VI) carcinogenesis.
| S-EPMC3259276 | biostudies-literature
Project description:BackgroundButyrate acts as a regulator in multiple inflammatory organ injuries. However, the role of butyrate in acute liver injury has not yet been fully explored. In the present study, we aimed to investigate the association between butyrate and lipopolysaccharide (LPS)-induced acute liver injury and the signaling pathways involved.MethodsLPS-induced acute liver injury was induced by intraperitoneal injection of LPS (5 mg/kg) in G-protein-coupled receptor 43 (GPR43)-knockout (KO) and wild-type female C57BL/6 mice. Sodium butyrate (500mg/kg) was administered intraperitoneally 30 min prior to LPS exposure. Liver injury was detected by serum markers, tissue morphology, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Pro-inflammatory-factor levels were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (RT-PCR). Cell models were first treated with sodium butyrate (4 μmol/mL), followed by LPS (1 μg/mL) half an hour later in GPR43 small interfering RNA (siRNA)-transfected or control RAW264.7 cells. Cell-inflammation status was evaluated through detecting pro-inflammatory-factor expression by RT-PCR and also through checking toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB)-element levels including TLR4, TRAF6, IKKβ, IкBα, phospho-IкBα, p65, and phospho-p65 by Western blot. The interaction between GPR43 and β-arrestin-2 was tested by co-immunoprecipitation.ResultsSodium butyrate reversed the LPS-induced tissue-morphology changes and high levels of serum alanine aminotransferase, aspartate transaminase, myeloperoxidase, TUNEL, and pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The ameliorating effect of sodium butyrate was weakened in GPR43-KO mice and GPR43 siRNA RAW264.7 cells, compared with those of GPR43-positive controls. Sodium butyrate downregulated some elements of the TLR4/NF-κB pathway, including phospho-IκBα and phospho-p65, in RAW264.7 cells. Increased interactions between GPR43 and β-arrestin-2, and between β-arrestin-2 and IкBα were observed.ConclusionSodium butyrate significantly attenuated LPS-induced liver injury by reducing the inflammatory response partially via the GPR43/β-arrestin-2/NF-κB signaling pathway.
| S-EPMC8128024 | biostudies-literature
Project description:The creatine kinase (CK) phosphagen system is fundamental to cellular energy homeostasis. Cardiomyocytes express three CK isoforms, namely the mitochondrial sarcomeric CKMT2 and the cytoplasmic CKM and CKB. We hypothesized that augmenting CK in vitro would preserve cell viability and function and sought to determine efficacy of the various isoforms. The open reading frame of each isoform was cloned into pcDNA3.1, followed by transfection and stable selection in human embryonic kidney cells (HEK293). CKMT2- CKM- and CKB-HEK293 cells had increased protein and total CK activity compared to non-transfected cells. Overexpressing any of the three CK isoforms reduced cell death in response to 18h hypoxia at 1% O2 followed by 2h re-oxygenation as assayed using propidium iodide: by 33% in CKMT2, 47% in CKM and 58% in CKB compared to non-transfected cells (P<0.05). Loading cells with creatine did not modify cell survival. Transient expression of CK isoforms in HL-1 cardiac cells elevated isoenzyme activity, but only CKMT2 over-expression protected against hypoxia (0.1% for 24h) and reoxygenation demonstrating 25% less cell death compared to non-transfected control (P<0.01). The same cells were not protected from doxorubicin toxicity (250nM for 48h), in contrast to the positive control. These findings support increased CK activity as protection against ischaemia-reperfusion injury, in particular, protection via CKMT2 in a cardiac-relevant cell line, which merits further investigation in vivo.
| S-EPMC5555628 | biostudies-other
Project description:Mutations in amyloid precursor protein (APP) and presenilin1 result in overproduction and accumulation of β-amyloid (Aβ) peptide, which has been shown to play an important role in Alzheimer's disease (AD) pathogenesis. Carvedilol, a nonselective β-adrenergic receptor blocker used for treatment for heart failure and hypertension, has displayed its neuroprotective capacity due to its antioxidant property. In this study, we investigated whether Carvedilol has a neuronal protective effect against endogenous Aβ neurotoxicity in mouse Neuro2a (N2a) cells transfected with Swedish amyloid precursor protein (Swe-APP) mutant and Presenilin exon9 deletion mutant (N2a/Swe.D9). Elevated levels of reactive oxygen species (ROS), protein carbonyls, and 4-HNE were found in N2a/Swe.D9 cells, which were ameliorated by administration of Carvedilol in a dose-dependent manner. In addition, the levels of ATP and mitochondrial membrane potential were reduced in N2a/Swe.D9 cells, which were restored by treatment with Carvedilol. N2a/Swe.D9 cells displayed increased vulnerability to H2O2-induced cell death and apoptosis, which could be attenuated by Carvedilol. Mechanistically, we found that Carvedilol prevented apoptosis signals through reducing cytochrome C release and the level of cleaved caspase-3. Taken together, our findings suggest a possible use of Carvedilol in AD treatment.
| S-EPMC6045552 | biostudies-literature
Project description:BackgroundDl-3-n-butylphthalide (NBP) is an important medial therapy for acute ischemic stroke in China. Recent studied have revealed that NBP not only rescued the loss of dopaminergic neurons in cellular and animal models of Parkinson's disease (PD), but also could improve motor symptoms in PD patients. However, the protective mechanism is not fully understood. P53 is a multifunctional protein implicated in numerous cellular processes, including apoptosis, DNA repair, mitochondrial functions, redox homeostasis, autophagy and protein aggregations. In PD, p53 integrated with various neurodegeneration-related signals inducing neuronal loss, indicating the suppression of P53 might be a promising target for PD treatment. Therefore, the purpose of the current study was to systemically screen new therapeutic targets of NBP in PD.MethodIn our study, we constructed mpp + induced N2A cells to investigate the benefit effect of NBP in PD. MTT assay was performed to evaluate the cell viability; TMT-based LC-MS/MS was applied to determine the different expressed proteins (DEPs) of NBP pretreatment; online bioinformatics databases such as DAVID, STRING, and KEGG was used to construe the proteomic data. After further analyzed and visualized the protein-protein interactions (PPI) by Cytoscape, DEPs were verified by western blot.ResultA total of 5828 proteins were quantified in the comparative proteomics experiments and 417 proteins were considered as DEPs (fold change > 1.5 and p < 0.05). Among the 417 DEPs, 140 were upregulated and 277 were downregulated in mpp + -induced N2A cells with NBP pretreatment. KEGG pathway analysis indicated that lysosome, phagosome, apoptosis, endocytosis and ferroptosis are the mainly enriched pathways. By using MCL clustering in PPI analysis, 48 clusters were generated and the subsequent KEGG analysis of the top 3 clusters revealed that P53 signaling pathway was recognized as the dominant pathway for NBP treatment.ConclusionNBP significantly relived mpp + -induced cell toxicity. The neuroprotective role of NBP was implicated with P53 signaling pathway in some extent. These findings will reinforce the understanding of the mechanism of NBP in PD and identify novel therapeutic targets.
| S-EPMC9809048 | biostudies-literature
Project description:Curcumin is extracted from the turmeric plant (Curcuma longa Linn.) and is widely used as a food additive and traditional medicine. The present study investigated the activity of curcumin against staurosporine (STS) toxicity in cell culture.Rat hippocampal neurons in primary culture were exposed to STS (20 μmol/L) and treated with curcumin (20 μmol/L). Cell viability was tested by MTT assay and reactive oxygen species (ROS) were measured using the MitoSOX™ red mitochondrial superoxide indicator. Western blot was used to assess changes in the levels of caspase-3 (Csp3), heat shock protein 70 (Hsp70) and Akt.The results showed that curcumin protects against STS-induced cytotoxicity in rat hippocampal neurons. Csp3, Hsp70, Akt and ROS activation may be involved in this protection.Curcumin could be a potential drug for combination with STS in cancer treatment to reduce the unwanted cytotoxicity of STS.
| S-EPMC5561927 | biostudies-other
Project description:Alzheimer's disease (AD) is a currently incurable neurodegenerative disorder and is the most common form of dementia in people over the age of 65 years. The predominant genetic risk factor for AD is the ?4 allele encoding apolipoprotein E (ApoE4). The secreted glycoprotein Reelin enhances synaptic plasticity by binding to the multifunctional ApoE receptors apolipoprotein E receptor 2 (Apoer2) and very low density lipoprotein receptor (Vldlr). We have previously shown that the presence of ApoE4 renders neurons unresponsive to Reelin by impairing the recycling of the receptors, thereby decreasing its protective effects against amyloid ? (A?) oligomer-induced synaptic toxicity in vitro. We showed that when Reelin was knocked out in adult mice, these mice behaved normally without overt learning or memory deficits. However, they were strikingly sensitive to amyloid-induced synaptic suppression and had profound memory and learning disabilities with very low amounts of amyloid deposition. Our findings highlight the physiological importance of Reelin in protecting the brain against A?-induced synaptic dysfunction and memory impairment.
| S-EPMC4652952 | biostudies-literature