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1.
J Agric Food Chem ; 72(17): 10076-10088, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38629202

ABSTRACT

This study aimed to explore antioxidant peptides derived from sturgeon (Acipenser schrenckii) ovaries that exhibit antiosteoporotic effects in oxidative-induced MC3T3-E1 cells. The F3-15 component obtained from sturgeon ovarian protein hydrolysates (SOPHs) via gel filtration and RP-HPLC significantly increased the cell survival rate (from 49.38 ± 2.88 to 76.26 ± 2.09%). Two putative antioxidant-acting peptides, FDWDRL (FL6) and FEGPPFKF (FF8), were screened from the F3-15 faction via liquid chromatography-tandem mass spectrometry (LC-MS/MS) and through prediction by computer simulations. Molecular docking results indicated that the possible antioxidant mechanisms of FL6 and FF8 involved blocking the active site of human myeloperoxidase (hMPO). The in vitro tests showed that FL6 and FF8 were equally adept at reducing intracellular ROS levels, increasing the activity of antioxidant enzymes, and protecting cells from oxidative injuries by inhibiting the mitogen-activated protein kinase (MAPK) pathway and activating the phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK-3ß) signaling pathway. Moreover, both peptides could increase differentiation and mineralization abilities in oxidatively damaged MC3T3-E1 cells. Furthermore, FF8 exhibited high resistance to pepsin and trypsin, showcasing potential for practical applications.


Subject(s)
Fish Proteins , Fishes , Osteoblasts , Ovary , Oxidative Stress , Peptides , Protein Hydrolysates , Animals , Protein Hydrolysates/chemistry , Protein Hydrolysates/pharmacology , Oxidative Stress/drug effects , Female , Mice , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoblasts/cytology , Peptides/chemistry , Peptides/pharmacology , Peptides/isolation & purification , Fish Proteins/chemistry , Fish Proteins/pharmacology , Fish Proteins/metabolism , Ovary/drug effects , Ovary/metabolism , Antioxidants/chemistry , Antioxidants/pharmacology , Cell Line , Cell Survival/drug effects , Molecular Docking Simulation , Reactive Oxygen Species/metabolism , Humans , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/chemistry , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Tandem Mass Spectrometry
2.
Crit Rev Food Sci Nutr ; : 1-21, 2024 Mar 17.
Article in English | MEDLINE | ID: mdl-38494796

ABSTRACT

Anthocyanins have become increasingly important to the food industry due to their colorant features and many health-promoting activities. Numerous studies have linked anthocyanins to antioxidant, anti-inflammatory, anticarcinogenic properties, as well as protection against heart disease, certain types of cancer, and a reduced risk of diabetes and cognitive disorders. Anthocyanins from various foods may exhibit distinct biological and health-promoting activities owing to their structural diversity. In this review, we have collected and tabulated the key information from various recent published studies focusing on investigating the chemical structure effect of anthocyanins on their stability, antioxidant activities, in vivo fate, and changes in the gut microbiome. This information should be valuable in comprehending the connection between the molecular structure and biological function of anthocyanins, with the potential to enhance their application as both colorants and functional compounds in the food industry.

3.
Int J Mol Sci ; 25(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38255916

ABSTRACT

Chicoric acid (CA) has been reported to exhibit biological activities; it remains unclear, however, whether CA could regulate colitis via modulation of the gut microbiota and metabolites. This study aimed to assess CA's impact on dextran sulfate sodium (DSS)-induced colitis, the gut microbiota, and metabolites. Mice were induced with 2.5% DSS to develop colitis over a 7-day period. CA was administered intragastrically one week prior to DSS treatment and continued for 14 days. The microbial composition in the stool was determined using 16S rRNA sequencing, while non-targeted metabolomics was employed to analyze the metabolic profiles of each mouse group. The results show that CA effectively alleviated colitis, as evidenced by an increased colon length, lowered disease activity index (DAI) and histological scores, and decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. CA intervention restored the structure of gut microbiota. Specifically, it decreased the abundance of Bacteroidetes and Cyanobacteria at the phylum level and Bacteroides, Rosiarcus, and unclassified Xanthobacteraceae at the genus level, and increased the abundance of unclassified Lachnospiraceae at the genus level. Metabolomic analysis revealed that CA supplementation reversed the up-regulation of asymmetric dimethylarginine, N-glycolylneuraminic acid, and N-acetylneuraminic acid, as well as the down-regulation of phloroglucinol, thiamine, 4-methyl-5-thiazoleethanol, lithocholic acid, and oxymatrine induced by DSS. Our current research provides scientific evidence for developing CA into an anti-colitis functional food ingredient. Further clinical trials are warranted to elucidate the efficacy and mechanism of CA in treating human inflammatory bowel disease (IBD).


Subject(s)
Caffeic Acids , Colitis , Gastrointestinal Microbiome , Succinates , Humans , Animals , Mice , Mice, Inbred BALB C , Dextran Sulfate/toxicity , RNA, Ribosomal, 16S/genetics , Colitis/chemically induced , Colitis/drug therapy
4.
Crit Rev Food Sci Nutr ; : 1-11, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38085004

ABSTRACT

Pulses have attracted much attention in the food industry due to their low cost, high yield, and high protein content, which promises to be excellent alternative protein sources. Recently, techniques for covalent and noncovalent binding of pulse proteins to polyphenols are expected to solve the problem of their poor protein functional properties. Additionally, these conjugates and complexes also show several health benefits. This review summarizes the formation of conjugates and complexes between pulse proteins and polyphenols through covalent and noncovalent binding and the impact of this structural change on protein functionalities and potential health benefits. Recent studies show that pulse protein functionalities can be influenced by polyphenol dose. This is mainly the case for adverse effects on solubility and enhancement in emulsifying capacity. Also, the conjugates/complexes exhibit antioxidant activity and can alter protein digestibility. The antioxidant activity of polyphenols could be retained after binding to proteins, while the effect on digestibility depends on the type or dosage of polyphenols. Considering the link between polyphenols and their potential health benefits, pulse polyphenols would be a good choice for producing the conjugates/complexes due to their low cost and proven potential benefits. Further studies on the structure-function-health benefits relationship of pulse protein-polyphenol conjugates and complexes are still required, as well as the validation of their application as functional foods in the food industry.

5.
Curr Res Food Sci ; 7: 100617, 2023.
Article in English | MEDLINE | ID: mdl-37881334

ABSTRACT

Dioxins are a group of chemicals not only regarded as highly toxic trace environmental contaminants, but also considered typical contaminants in food. Dioxins spread across the ecosystem after factory manufacture, contaminate the soil and vegetation before either directly or indirectly entering the food chain through meat products, dairy products, and aquatic products. The compound in question poses a challenge for metabolic processes within the human body, due to its intricate mechanism for inducing diseases. Therefore, it presents a significant risk and is largely undisclosed. Dioxins are mainly exposed to humans by water, food, and air, as well as inducing organ failure and metabolic disorders through but not limited to the activation of aryl hydrocarbon receptors (AhR). As a notorious compound in the family of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibits long-term toxic effects on diverse organs, which induces continuous metabolic disorders. This review discussed the mechanisms of TCDD-associated metabolic syndrome. The expression of the cytochrome P450 subfamily transfers TCDD into liver, promotes its accumulation in fat tissue, and affects cholesterol metabolism. This process also alters the glucose tolerance of the human organism, disrupting glucose metabolism. It can also elicit cardiovascular pathogenesis, exacerbate liver fibrosis and neuronal death. The long-term metabolic impact of this effect is found to be sex-related. This review summarized the toxicity of TCDD on the human metabolism system and discussed the plausible correlation between TCDD and five metabolic disorders, which helped offer novel insights for future research and therapeutic interventions for these ailments.

6.
Curr Res Food Sci ; 7: 100534, 2023.
Article in English | MEDLINE | ID: mdl-37441166

ABSTRACT

Dihydrxytetraphenylmethane, also known as Bisphenol BP (BPBP), has been increasingly used in industrial production and more frequently detected in the environment as an alternative plasticizer of BPA. However, there are no reports about BPBP in food safety or its effects on cellular lipogenesis. The purpose of this research was to investigate the influence and potential mechanisms of BPBP on adipogenesis in 3T3-L1 cells. Cells were treated with 4 concentrations (0.01, 0.1, 1, and 10 µM) of BPBP and the results showed that treatment with at low concentrations (0.01 µM) promoted cell fat differentiation and triglyceride accumulation. RNA-seq data showed that a total of 370 differentially expressed genes between control and the low-dose BPBP-treated group were determined, including 227 upregulated genes and 143 downregulated genes. Some key genes related to adipocyte differentiation and adipogenesis were significantly enriched after BPBP treatment, including PPAR-γ, Adipoq, Nr1h3 and Plin1. Pathway analyses suggest that the activation of PPAR-γ signaling pathway may be key for BPBP to promote adipocyte differentiation and fat accumulation. Our work provides evidence for the potential obesogenic effect of BPBP and may call for further research on the safety of the chemical in food products.

7.
Crit Rev Food Sci Nutr ; : 1-14, 2023 Jun 07.
Article in English | MEDLINE | ID: mdl-37287270

ABSTRACT

Osmanthus fragrans (O. fragrans) has been cultivated in China for over 2,500 years as a traditional fragrant plant. Recently, O. fragrans has drawn increasing attention due to its unique aroma and potential health benefits. In this review, the aroma and functional components of O. fragrans are summarized, and their biosynthetic mechanism is discussed. The beneficial functions and related molecular mechanism of O. fragrans extract are then highlighted. Finally, potential applications of O. fragrans are summarized, and future perspectives are proposed and discussed. According to the current research, O. fragrans extracts and components have great potential to be developed into value-added functional ingredients with preventive effects on certain chronic diseases. However, it is crucial to develop efficient, large-scale, and commercially viable extraction methods to obtain the bioactive components from O. fragrans. Furthermore, more clinical studies are highly needed to explore the beneficial functions of O. fragrans and guide its development into functional food products.

8.
FASEB J ; 37(7): e23009, 2023 07.
Article in English | MEDLINE | ID: mdl-37273180

ABSTRACT

Human and animal studies support that consuming a high level of linoleic acid (LA, 18:2ω-6), an essential fatty acid and key component of the human diet, increases the risk of colon cancer. However, results from human studies have been inconsistent, making it challenging to establish dietary recommendations for optimal LA intake. Given the importance of LA in the human diet, it is crucial to better understand the molecular mechanisms underlying its potential colon cancer-promoting effects. Using LC-MS/MS-based targeted lipidomics, we find that the cytochrome P450 (CYP) monooxygenase pathway is a major pathway for LA metabolism in vivo. Furthermore, CYP monooxygenase is required for the colon cancer-promoting effects of LA, since the LA-rich diet fails to exacerbate colon cancer in CYP monooxygenase-deficient mice. Finally, CYP monooxygenase mediates the pro-cancer effects of LA by converting LA to epoxy octadecenoic acids (EpOMEs), which have potent effects on promoting colon tumorigenesis via gut microbiota-dependent mechanisms. Overall, these results support that CYP monooxygenase-mediated conversion of LA to EpOMEs plays a crucial role in the health effects of LA, establishing a unique mechanistic link between dietary fatty acid intake and cancer risk. These results could help in developing more effective dietary guidelines for optimal LA intake and identifying subpopulations that may be especially vulnerable to LA's negative effects.


Subject(s)
Colonic Neoplasms , Linoleic Acid , Humans , Mice , Animals , Linoleic Acid/pharmacology , Linoleic Acid/metabolism , Chromatography, Liquid , Tandem Mass Spectrometry , Eicosanoids , Cytochrome P-450 Enzyme System/metabolism , Diet , Colonic Neoplasms/etiology
10.
J Agric Food Chem ; 71(24): 9419-9428, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37294270

ABSTRACT

Chondroitin sulfate (CS) is a special bioactive substance with lipid metabolism regulation functions; its molecular mechanisms, however, need further study. This study aimed to study the role of gut microbiota and liver metabolome in the anti-obesity effects of CS. The results demonstrated that CS significantly reduced body weight gain and alleviated insulin resistance and dyslipidemia induced by high-fat diet treatment. Moreover, CS interestingly increased the content of Firmicutes in intestinal microbiota. Further studies showed that there were 11 different metabolites involved in metabolic pathways, including the unsaturated fatty acid biosynthesis pathway, primary bile acid biosynthesis, and taurine and hypotaurine metabolism. In addition, Spearman's correlation analysis indicated that the anti-obesity effect of CS is closely related to liver metabolic regulation. Overall, these results provide a possible molecular mechanism by which CS reduces body weight and lipid accumulation.


Subject(s)
Gastrointestinal Microbiome , Animals , Mice , Mice, Obese , Chondroitin Sulfates/metabolism , Diet, High-Fat/adverse effects , Obesity/drug therapy , Obesity/genetics , Obesity/metabolism , Liver/metabolism , Body Weight , Metabolome , Mice, Inbred C57BL
11.
Crit Rev Food Sci Nutr ; 63(9): 1155-1169, 2023.
Article in English | MEDLINE | ID: mdl-36394558

ABSTRACT

Barley is one of the world's oldest cereal crops forming an important component of many traditional diets. Barley is rich in a variety of bioactive phytochemicals with potentially health-promoting effects. However, its beneficial nutritional attributes are not being fully realized because of the limited number of foods it is currently utilized in. It is therefore crucial for the food industry to produce novel barley-based foods that are healthy and cater to customers' tastes. This article reviews the nutritional and functional characteristics of barley, with an emphasis on its ability to improve glucose/lipid metabolism. Then, recent trends in barley product development are discussed. Finally, current limitations and future research directions in glucolipid modulation mechanisms and barley bioprocessing are discussed.


Subject(s)
Hordeum , Hordeum/chemistry , Dietary Supplements , Nutrients , Diet , Edible Grain
12.
Front Nutr ; 9: 1014322, 2022.
Article in English | MEDLINE | ID: mdl-36211482
13.
Crit Rev Food Sci Nutr ; : 1-26, 2022 Oct 31.
Article in English | MEDLINE | ID: mdl-36315047

ABSTRACT

According to the World Health Organization, cardiovascular disease (CVD) has become a major cause of chronic illness around the globe. It has been reported that soy-based fermented food (SFF) is very effective in preventing thrombus (one of the most important contributing factors to CVD), which are mainly attributed to the bioactive substances, especially the fibrinolytic enzymes (FE) generated by microorganisms during the fermentation process of soybean food. This paper therefore mainly reviewed the microbial fibrinolytic enzymes (MFE) from SFF. We first discuss the use of microbial fermentation to produce FE, with an emphasis on the strains involved. The production, purification, physicochemical properties, structure-functional attributes, functional properties and possible application of MFE from SFF are then discussed. Finally, current limitations and future perspectives for the production, purification, and the practical application of MFE are discussed. MFE from SFF pose multiple health benefits, including thrombolysis, antihypertension, anti-inflammatory, anti-hyperlipidemia, anticancer, neuroprotective, antiviral and other activities. Therefore, they exhibit great potential for functional foods and nutraceutical applications, especially foods with CVDs prevention potential.

14.
Chemosphere ; 307(Pt 4): 135960, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35961445

ABSTRACT

Thiram has been widely used in agriculture and may invades the food chain, posing a threat to human health. In this research, a label-free electrochemical cell-based biosensor was presented for in vitro toxicity assessment of thiram. HepG2 cells were cultured on poly-l-lysine@gold nano-flowers functionalized indium tin oxide coated glass electrode (PLL@AuNFs/ITO) to serve as biorecognition elements. AuNFs were electrodeposited on ITO to provide an enlarged specific surface area and benefited the output signal amplification. PLL was selected as an effective biocompatible coating material to facilitate cell adhesion and proliferation, thereby realizing one-step recording of electrochemical signals from thiram-treated cells. With the aid of the differential pulse voltammetry method, the fabricated biosensor was applied to assess the cytotoxicity of thiram. Results showed that the cytotoxicity measured by the fabricated biosensor exhibited a linear relationship related to thiram concentration ranging from 5 to 50 µM with a detection limit of 2.23 µM. The IC50 of thiram obtained by the biosensor was 29.5 µM, which was close to that of conventional MTT assay (30.8 µM). The effects of thiram on HepG2 cells were also investigated via SEM and flow cytometry. Meanwhile, the proposed biosensor was used to evaluate the toxicity of thiram in fruit samples. Results indicated that the toxicity of thiram cannot be ignored even at a low residual concentration in food (≤5 mg/kg). In conclusion, the developed sensor showed excellent sensitivity, stability, and reliability, which provided a great capacity for the convenient toxicity evaluation of thiram residue in food.


Subject(s)
Biosensing Techniques , Thiram , Biosensing Techniques/methods , Electrochemical Techniques/methods , Electrodes , Gold/chemistry , Gold/toxicity , Humans , Polylysine , Reproducibility of Results
15.
Foods ; 11(13)2022 Jun 29.
Article in English | MEDLINE | ID: mdl-35804751

ABSTRACT

Soybean oil, which has high abundance of linoleic acid (LA, 18:2ω-6), is the most commonly consumed edible oil. Recent studies support that a high dietary intake of LA is linked with increased risks of developing colonic inflammation and colon cancer. Here we studied the effects of the genetically modified Plenish® soybean oil, which has low abundance of LA as well as α-linolenic acid (ALA, 18:3ω-3), on development of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon tumorigenesis in mice. Compared with a diet rich in traditional soybean oil, administration of a diet enriched with the Plenish oil has little impact on AOM/DSS-induced colon tumorigenesis, colonic infiltration of immune cells, expressions of inflammatory genes, and tumor markers. These results suggest that the traditional and the Plenish soybean oils have similar effects on development of AOM/DSS-induced colon cancer in mice.

16.
Curr Res Food Sci ; 5: 857, 2022.
Article in English | MEDLINE | ID: mdl-35647561
17.
Pestic Biochem Physiol ; 184: 105114, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35715053

ABSTRACT

Previously, deltamethrin (a Type-II pyrethroid) has been reported to increase triglyceride (fat) accumulation in adipocytes, while its underlying molecular mechanism is not fully determined. The aim of this study was to further investigate the molecular mechanisms of deltamethrin induced fat accumulation in murine 3T3-L1 adipocytes. Consistent to previous reports, deltamethrin (10 µM) significantly promoted adipogenesis in 3T3-L1 adipocytes. RNA sequencing (RNA-seq) results showed that 721 differentially expressed genes (DEGs) were identified after deltamethrin treatment, involving in 58 Functional groups of Gene Ontology (GO) and 255 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Several key functional groups regulating adipogenesis, such as fat cell differentiation (Igf1, Snai2, Fgf10, and Enpp1) and cytosolic calcium ion concentration (Nos1, Cxcl1, and Ngf) were significantly enriched. Collectively, these results suggest that the promotion of adipogenesis by deltamethrin was attributed to an obesogenic global transcriptomic response, which provides further understanding of the underlying mechanisms of deltamethrin-induced fat accumulation.


Subject(s)
Adipocytes , Pyrethrins , 3T3-L1 Cells , Adipogenesis/genetics , Animals , Gene Expression Profiling , Mice , Nitriles , Pyrethrins/metabolism , Pyrethrins/toxicity
18.
Curr Res Food Sci ; 5: 677-686, 2022.
Article in English | MEDLINE | ID: mdl-35434649

ABSTRACT

In this study, blueberry anthocyanins, gelatin and Fe2+ were incorporated into zein matrix via electrospinning method to prepare colorimetric indicator films for monitoring milk freshness. Gelatin and Fe2+ were incorporated into the film to improve visual discrimination of indicator films' color changes in milk with different freshness degrees and in solution with pH 3-7. Results of SEM, FT-IR and XRD showed that there were intermolecular hydrogen bonds among components, which associated with the larger color difference of indicator films. UV-vis spectral analysis showed that blueberry anthocyanin solutions containing both gelatin and Fe2+ displayed the highest intensity absorption peaks. The optimal ability to distinguish the pH (3-7) of solutions was presented by the indicator film incorporating gelatin (1% (w/v)) and Fe2+ (0.07 mg/mL). Gelatin and Fe2+ increased the color-responsive sensitivity of the indicator film to pH. The film could be successfully used to detect the freshness of milk, whose color changes were visually perceivable: from purple black (fresh milk) to royal purple (spoiling milk) and then to violet red (spoiled milk). The color parameters (L*, a*, R, G and B) of the film revealed a high correlation with the pH/acidity of the milk during storage. The successful application of the indicator film embedding gelatin and Fe2+ for monitoring milk quality changes indicated that the addition of special substances could provide great potential for monitoring freshness and preparing intelligent packaging of food.

19.
Phytomedicine ; 99: 153969, 2022 May.
Article in English | MEDLINE | ID: mdl-35183930

ABSTRACT

BACKGROUND: SiNiSan, a Traditional Chinese Medicine containing Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, and Radix Glycyrrhizae, has been shown to be clinically effective in treating liver damage, its underlying molecular mechanisms however remains unclear. PURPOSE: The aim of the current study was to understand the molecular mechanisms of SiNiSan in the treatment of liver damage utilizing mice and cell culture models. METHODS: Here, mice were gavaged with 0.2% CCl4 to obtain acute liver injury model and with alcohol to obtain chronic liver injury model. H&E staining was performed to detect liver histomorphology. HPLC-MS was performed to analyze the composition of SiNiSan decoction and SiNiSan-medicated serum (SMS). In addition, western blots were done to analyze the representative protein expression in Wnt/ß-catenin signaling. Immunofluorescence staining was done to analyze the protein levels in WB-F344 cells. Finally, in an attempt to measure the influence of SiNiSan on liver regeneration in rats, we constructed a rats partial hepatectomy models. RESULTS: We demonstrated that SiNiSan treatment mitigated liver damage in mice, as evidenced by the decrease in serum AST and ALT levels, as well as improved liver tissue morphology. HPLC-MS results showed that SMS contained a variety of components from the SiNiSan decoction. Next, our results showed that SMS reduced the expression of α-fetoprotein (AFP) and enhanced the expression of albumin (ALB) and cytokeratin 19 (CK19) in WB-F344 cells. Further, SMS treatment induced the accumulation of ß-catenin. After 14 days of SMS treatment, ß-catenin protein underwent nuclear translocation and bound to the LEF1 receptor in the nucleus, which regulated c-Myc and Cyclin D1 factors to activate Wnt/ß-catenin signaling and promoted differentiation of WB-F344 cells. In addition, we demonstrated that SiNiSan increased liver regeneration in rat hepatectomy. CONCLUSION: Collectively, the current study revealed that SiNiSan alleviated the acute liver injury induced by CCl4 as well as the chronic liver damage triggered by alcohol and sucrose in vitro. Concurrently, SMS treatment induced hepatic stem cell differentiation by activating Wnt/ß-catenin signaling in vivo. Further study showed that SiNiSan promoted the regeneration of rats liver. The current study provides a theoretical basis for the clinical treatment of liver-related diseases with SiNiSan.

20.
Toxicology ; 465: 153052, 2022 01 15.
Article in English | MEDLINE | ID: mdl-34838597

ABSTRACT

Bisphenol-A (BPA), an environmental endocrine disruptor, is toxic to the central nervous system. Although recent studies have shown BPA-induced neurotoxicity, it is far from clear what precisely epigenetic mechanisms are involved in BPA-induced cognitive deficits. In this study, pheochromocytoma (PC12) cells were treated with BPA at 1 µM for 36 h in vitro. In vivo, C57BL/6 mice were administered to BPA at a dose of 1 mg/kg/day for 10 weeks. The results showed that 1 µM BPA exposure for 36 h impaired neurite outgrowth of PC12 cells through decreasing the primary and secondary branches. Besides, BPA exposure decreased the level of Ac-H3K9 (histone H3 Lys9 acetylation) by upregulating the expression of HDAC2 (histone deacetylases 2) in PC12 cells. Furthermore, treatment of both TSA (Trichostatin A, inhibitor of the histone deacetylase) and shHDAC2 plasmid (HDAC2 knockdown construct) resulted in amelioration neurite outgrowth deficits induced by BPA. In addition, it was shown that repression of HDAC2 could markedly rescue the spine density impairment in the hippocampus and prevent the cognitive impairment caused by BPA exposure in mice. Collectively, HDAC2 plays an essential role in BPA-induced neurotoxicity, which provides a potential molecular target for medical intervention.


Subject(s)
Benzhydryl Compounds/toxicity , Dendritic Spines/drug effects , Environmental Pollutants/toxicity , Hippocampus/drug effects , Histone Deacetylase 2/metabolism , Neurites/drug effects , Neurotoxicity Syndromes/etiology , Phenols/toxicity , Animals , Behavior, Animal/drug effects , Cognition/drug effects , Dendritic Spines/enzymology , Dendritic Spines/pathology , Female , Hippocampus/enzymology , Hippocampus/pathology , Hippocampus/physiopathology , Histone Deacetylase 2/genetics , Male , Maze Learning/drug effects , Mice, Inbred C57BL , Neurites/enzymology , Neurites/pathology , Neuronal Outgrowth/drug effects , Neurotoxicity Syndromes/enzymology , Neurotoxicity Syndromes/pathology , Neurotoxicity Syndromes/physiopathology , PC12 Cells , Rats , Up-Regulation
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