JOURNAL OF PROTEOME RESEARCH
·
2024
·
IF 3.8
Huanying Pang,Weijie Zhang,Xuelian Lin,Fuyuan Zeng,Xing Xiao,Zhiqing Wei,Shi Wang,Jichang Jian,Na Wang,Wanxin Li
Protein succinylation modification is a common post-translational modification (PTM) that plays an important role in bacterial metabolic regulation. In this study, quantitative analysis was conducted on the succinylated proteome of wild-type and florfenicol-resistant Vibrio alginolyticus to investigate the mechanism of succinylation regulating antibiotic resistance. Bioinformatic analysis showed that the differentially succinylated proteins were mainly enriched in energy metabolism, and it was found that the succinylation level of phosphoenolpyruvate carboxyl kinase (PEPCK) was highly expressed in the florfenicol-resistant strain. Site-directed mutagenesis was used to mutate the lysine (K) at the succinylation site of PEPCK to glutamic acid (E) and arginine (R), respectively, to investigate the function of lysine succinylation of PEPCK in the florfenicol resistance of V. alginolyticus. The detection of site-directed mutagenesis strain viability under florfenicol revealed that the survival rate of the E mutant was significantly higher than that of the R mutant and wild type, indicating that succinylation modification of PEPCK protein may affect the resistance of V. alginolyticus to florfenicol. This study indicates the important role of PEPCK during V. alginolyticus antibiotic-resistance evolution and provides a theoretical basis for the prevention and control of vibriosis and the development of new antibiotics.
研究领域:
微生物学
·
分子生物学
·
药理学
·
蛋白质组学
✓ 已验证
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2026
·
IF 4.2
Lingjun Xie,Chushun Yi,Zhentao Ma,Songlin Luo,Shunqiang Wei,Xuemin Wei,Yinghui Wang,Aiguo Huang
Genipin inhibits WSSV replication in gill, hepatopancreas and muscle tissues in shrimp. • Genipin inhibits the expression of VP19, VP24, VP26, and VP28 in Drosophila S2 cells. • WSSV infection reprograms host metabolism to support viral replication. • Genipin exerts a bidirectional, dose-dependent modulation of host metabolism in shrimp. • PC and PEPCK are potential antiviral targets of genipin. White spot syndrome virus (WSSV) is the most devastating pathogen in shrimp aquaculture, causing massive economic losses worldwide. Current control strategies are limited due to the lack of adaptive immunity in crustaceans. In this study, the antiviral mechanism of genipin, a natural compound with known anti-WSSV activity, was investigated using a dual proteomic approach in Pacific whiteleg shrimp ( Litopenaeus vannamei ). In vitro fluorescence analysis confirmed that genipin specifically suppressed the expression of WSSV structural proteins. Through a four-group design (control, WSSV-infected, genipin-treated, and genipin-treated infected), 715 “drug-reversed” proteins were identified, whose WSSV-induced dysregulation was significantly restored by genipin. Protein set enrichment analysis and over-representation analysis revealed that genipin globally suppresses ribosome biogenesis and central carbon metabolic pathways, including the TCA cycle--pathways critical for viral replication. A concentration-gradient experiment further revealed differential regulation: genipin dose-dependently down-regulated cytoskeletal and metabolic components while up-regulating stress-responsive and adhesion modules, forming a “core response network” (CRN). Integrative cross-dataset analysis pinpointed two metabolic gatekeepers, pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK), which exhibited hallmark virus-induced up-regulation and genipin-mediated reversal. Both enzymes occupy central positions linking the CRN to core metabolic pathways, suggesting a signal-metabolic coupling mechanism. Collectively, these results establish genipin as an agent that dismantles WSSV's metabolic support system potentially through modulation of PC and PEPCK, providing a promising strategy for combating viral diseases in shrimp aquaculture.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Huashan Gao,Linlin Ding,Rui Liu,Xinhua Zheng,Xichao Xia,Fuan Wang,Jinxu Qi,Weishuang Tong,Yuanhao Qiu
Anoectochilus roxburghii is a traditional herb in China that can be potentially used to treat diabetes. A novel polysaccharide ARLP-W was isolated from Anoectochilus roxburghii by chromatography on DEAE-52 cellulose. Chemical analysis indicated that ARLP-W (8.1 × 10 4 Da) was mainly composed of mannose and glucose. The main linkages of glycosidic bonds of ARLP-W were β-1, 4-Manp and α-1, 4-Glcp. The terminal Glcp was connected to Manp-via O-3. RT-qPCR and western blotting analysis showed that ARLP-W caused a significant reduction in the levels of the key gluconeogenesis enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) in the liver. The results of the insulin resistance tests indicated that ARLP-W increased glucose absorption. These results indicate that ARLP-W has a good therapeutic effect on type 2 diabetes and can assist with further development and application treatment of diabetes.
研究领域:
药理学
·
生物化学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
IF 2.5
Li Wang,Yi-Xiao Chen,Xin-Jing Meng,Hai-Yang Liang,Ya-Dan Zhang,Hui-Hui Zhou,Yu-Hang Liu,Xiao-Yu Chen,Zhen-Hua Liu,Shi-Ming Li,Wen-Yi Kang
Patrinia punctiflora is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the isolation of six iridoids, which were previously unreported compounds, patriscabioins P U ( 1–6 ). Their structures were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Among them, compound 5 was screened to evaluate its insulin resistance activity on an IR-HepG-2 cell model. Compound 5 had no cytotoxicity compared with the control group and could promote glucose uptake in IR-HepG-2 cells. Through further mechanism studies, the undescribed compound 5 could increase the expression levels of PI-3 K, p -AKT, GLUT4 and p -GSK3 β proteins. Moreover, the expression of PEPCK and G6Pase proteins, which are key gluconeogenic enzymes, was also inhibited. Thus, compound 5 promotes the transfer of GLUT4 to the plasma membrane by activating the PI-3 K/AKT signaling pathway, at the same time, promotes glycogen synthesis and inhibits the onset of gluconeogenesis, which in turn ameliorates insulin resistance.
研究领域:
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Feier Cheng,Lin Han,Yao Xiao,Chuanying Pan,Yunlong Li,Xinhui Ge,Yao Zhang,Shaoqing Yan,Min Wang
d-chiro-Inositol (DCI) is a biologically active component found in tartary buckwheat, which can reduce hyperglycemia and ameliorate insulin resistance. However, the mechanism underlying the antidiabetic effects of DCI remains largely unclear. This study investigated the effects and underlying molecular mechanisms of DCI on hepatic gluconeogenesis in mice fed a high fat diet and saturated palmitic acid-treated hepatocytes. DCI attenuated free fatty acid uptake by the liver via lipid trafficking inhibition, reduced diacylglycerol deposition, and hepatic PKCε translocation. Thus, DCI could improve insulin sensitivity by suppressing hepatic gluconeogenesis. Subsequent analyses revealed that DCI decreased hepatic glucose output and the expression levels of PEPCK and G6 Pase in insulin resistant mice through PKCε-IRS/PI3K/AKT signaling pathway. Likewise, such effects of DCI were confirmed in HepG2 cells with palmitate-induced insulin resistance. These findings indicate a novel pathway by which DCI prevents hepatic gluconeogenesis, reduces lipid deposition, and ameliorates insulin resistance via regulation of PKCε-PI3K/AKT axis.
研究领域:
药理学
·
内分泌学
·
分子生物学
·
代谢紊乱
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Yue Leng,Li Ren,Shu Niu,Tiehua Zhang,Jie Zhang
The endocrine disruptive capability of plasticizers to activate nuclear receptors has attracted great interest. This study is aimed to assess the potential glucocorticoid effects of metabolites of plasticizers. The effects of metabolites of plasticizers on the transcriptional activity of glucocorticoid receptor (GR) were investigated using reporter gene assays. All of them failed to exhibit agonistic/antagonistic effects on GR. However, a combination of dexamethasone and monobutyl phthalate (MBP) could synergistically activate GR. MBP combined with dexamethasone also enhanced GR nuclear translocation by Western blot , while mifepristone restrained GR cytoplasmic-to-nuclear translocation. MBP co-treated with dexamethasone resulted in synergistic induction of PEPCK and MKP-1 gene expression by real-time PCR and PEPCK protein level by Western blot. Furthermore, the carboxyl and ester groups of MBP have influences on the charge distribution of MBP, leading to change of electrostatic interactions between MBP and GR by calculations on electronic properties. Both hydrophobic and hydrogen bonding interactions play a crucial role in the stabilization between MBP and GR conducted by molecular docking and dynamics simulation. This work confirms that GR could remain stable upon binding to MBP. In conclusion, dexamethasone and MBP could synergistically activate GR, resulting in synergetic enhancement of subsequent GR-mediated endocrine disrupting effect.
研究领域:
毒理学
·
内分泌学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2022
·Vol. 10
·期 7
·2455-2469
·
IF 3.553
Xiaoyu Chen,Hongyuan Zhao,Fanqiang Meng,Libang Zhou,Xinyi Pang,Zhaoxin Lu,Yingjian Lu
Surfactin, produced by Bacillus amyloliquefaciens fmb50, was used to treat insulin-resistant (IR) hepatocyte. It was found that surfactin increased glucose consumption in insulin-resistant HepG2 (IR-HepG2) cells and ameliorated IR by increasing glucose transporter 4 (GLUT4) protein expression and AMP-activated protein kinase (AMPK) mRNA expression, promoting GLUT4 translocation and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in IR-HepG2 cells. Meanwhile, surfactin downregulated protein expression of phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase), further inhibiting hepatic gluconeogenesis. In addition, surfactin played important roles in eliminating reactive oxygen species (ROS), improving mitochondrial dysfunction, and inhibiting proinflammatory mediators. We observed that surfactin promoted glucose consumption, meanwhile increased translocation and protein expression of GLUT4 in Caco-2 cells. These results confirmed the conclusion in hepatic cells. Furthermore, surfactin supplement decreased body weight, food intake, and fasting blood glucose of type 2 diabetes mellitus (T2DM) mice induced by streptozotocin (STZ)/high-fat diet (HFD). Our data indicated that surfactin ameliorated insulin resistance and lowered blood glucose in intro and in vivo.
研究领域:
药理学
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms
·
2015
·
IF 6.332
Lushan Yu,Zhangting Wang,Minmin Huang,Yingying Li,Kui Zeng,Jinxiu Lei,Haihong Hu,Baian Chen,Jing Lu,Wen Xie,Su Zeng
The constitutive androstane receptor (CAR) is a key sensor in xenobiotic detoxification and endobiotic metabolism. Increasing evidence suggests that CAR also plays a role in energy metabolism by suppressing the hepatic gluconeogenesis and lipogenesis . In this study, we investigated the effects of two evodia alkaloids, rutaecarpine ( Rut ) and evodiamine ( Evo ), on gluconeogenesis and lipogenesis through their activation of the human CAR (hCAR). We found that both Rut and Evo exhibited anti-lipogenic and anti-gluconeogenic effects in the hyperlipidemic HepG2 cells. Both compounds can potently activate hCAR, and treatment of cells with hCAR antagonists reversed the anti-lipogenic and anti-gluconeogenic effects of Rut and Evo . The anti-gluconeogenic effect of Rut and Evo was due to the CAR-mediated inhibition of the recruitment of forkhead box O1 (FoxO1) and hepatocyte nuclear factor 4α (HNF4α) onto the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene promoters. In vivo, we showed that treatment of mice with Rut improved glucose tolerance in a CAR-dependent manner. Our results suggest that the evodia alkaloids Rut and Evo may have a therapeutic potential for the treatment of hyperglycemia and type 2 diabetes. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors : New Tricks for An Old Dog, edited by Dr. Wen Xie.
研究领域:
药理学
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2023
·
IF 8.1
Qiannan Zhao,Jinyi Yang,Jiahui Li,Lei Zhang,Xiaohai Yan,Tianli Yue,Yahong Yuan
Phenolics of mulberry ( Morus alba L.) leaves (MLs) have potential anti-diabetic effects, but they may be chemically modified during gastrointestinal digestion so affect their biological activity. In this study, an in vitro digestion model coupled with Caco-2 monolayer and Caco-2/insulin-resistant HepG2 coculture model were used to study the transport and hypoglycemic effects of phenolics in raw MLs (U-MLs) and solid-fermented MLs (F-MLs). The results of LC-MS/MS analysis showed that the Papp (apparent permeability coefficient, 10 –6 cm/s) of phenolics in digested MLs ranged from 0.002 ± 0.00 (quercetin 3- O -glucoside) to 60.19 ± 0.67 (ferulic acid), indicating higher phenolic acids absorbability and poor flavonoids absorbability. The Papp values of phenolic extracts of F-MLs in Caco-2 monolayer were significantly higher (p > 0.05) than that of U-MLs. Digested phenolic extracts inhibited the activities of sucrase (60.13 ± 2.03%) and maltase (82.35 ± 0.78%) and decreased 9.28 ± 0.84% of glucose uptake in Caco-2 monolayer. Furthermore, a decrease in the mRNA expression of glucose transporters SGLT1 (0.64 ± 0.18), GLUT2 (0.14 ± 0.02) and the sucrase-isomaltase (0.59 ± 0.00) was observed. In Caco-2/insulin-resistant HepG2 co-culture model, phenolic extracts regulated glucose metabolism by up-regulating the mRNA expressions of IRS1 (9.32-fold), Akt (17.07-fold) and GYS2 (1.5-fold), and down-regulating the GSK-3β (0.22-fold), PEPCK (0.49-fold) and FOXO1 (0.10-fold) mRNA levels. Both U-MLs and F-MLs could improve glucose metabolism, and the partial least squares (PLS) analysis showed that luteoforol and p -coumaric acid were the primary phenolics that strongly correlated with the hypoglycemic ability of MLs. Results suggested that phenolics of MLs can be used as dietary supplements to regulate glucose metabolism.
研究领域:
药理学
·
营养学
·
生物化学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 45
·期 7
·e13771
·
IF 2.72
Chao Xin,Mengya Zhao,Jiahui Wang,Zhenyu Wang
Hawthorn berry has been proved hypoglycemic effect due to the presence of some α-glucosidase inhibitors. Herein, screening and identifying of α-glucosidase inhibitors from hawthorn berry were conducted, and the results showed polyphenols mainly containing quercetin (74.58%) and hyperioside (9.58%) were responsible for its bioactivity. In order to enhance the hypoglycemic effect, the combined glucose-lowering complex (DEH) consisting of hawthorn polyphenols, D-chiro-inositol (DCI), and epigallocatechin gallate (EGCG) was prepared, where three ingredients exerted the synergistic hypoglycemic effect to enhance glucose consumption and glycogen levels and inhibit hepatic gluconeogenesis in IR-HepG2 cells. In STZ/HFD-induced mice, DEH effectively improved insulin resistance, reduced fasting blood glucose (FBG) and hepatic gluconeogenesis, and increased hepatic glycogen synthesis and storage via down-regulation of PI3K/Akt/FOXO1-mediated PEPCK and G6Pase and up-regulation of PI3K/Akt/GSK3-mediated GS activation in the liver. In summary, these findings indicate that DEH is a potential novel strategy for the treatment of type 2 diabetes. Practical applications Glucose-lowering complex (DEH) with superior hypoglycemic effect, can effectively improve the insulin resistance, reduce the fasting blood glucose, hepatic gluconeogenesis and increase the hepatic glycogen synthesis and storage in mice, which represents a potential novel strategy for the treatment of type 2 diabetes.
研究领域:
药理学
·
糖尿病研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2019
·Vol. 9
·期 1
·1-13
·
IF 4.011
Xu Shuwen,Wang Gang,Peng Wei,Xu Yandi,Zhang Yu,Ge Ying,Jing Yue,Gong Zhunan
Type 2 diabetes (T2D) with high morbidity and mortality is characterized by abnormal glucose and lipid metabolism due in part to insulin resistance in liver, which lead to elevated hyperglycemia and hyperlipidemia. This study sough to explore the effects of corosolic acid (CA) in different T2D models and explored the underlying mechanism. Separated from Eriobotrya japonica leaves, CA purity was above 95% measured by a HPLC method. Compared with cAMP and DEX induced T2D HepG2 model, CA significantly stimulated glucose consumption and improved glycogen accumulation by inhibiting PEPCK mRNA expression. And in cAMP and DEX induced T2D zebrafish model, CA reduced glycogen degradation and increased glucose consumption by regulating some key enzymes in carbon metabolism including GLUT1, GLUT2, GLUT3, LDHA, LDHB, GP, G6Pase, GYS1, and PFKFB3. In addition, insulin receptor signals were also involved in CA-regulated hypoglycemic action. Furthermore, in STZ-induced T2D rat model, compared with diabetic control groups, CA remarkably downregulated the levels of serum lipid, blood glucose, ICAM-1, malonaldehyde and insulin resistance index, while upregulated SOD activity and impaired glucose tolerance. In a conclusion, CA can regulate glucose and lipid metabolic adaptation in T2D like HepG2, zebrafish and rat models partly through reducing inflammation and oxidative stress and suppressing PEPCK .
研究领域:
药理学
·
糖尿病研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Xu-guang Zhang,Ai-xia Liu,Yu-xin Zhang,Ming-yan Zhou,Xiang-yi Li,Ming-hai Fu,Yi-peng Pan,Jian Xu,Jun-qing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). Aim of the study : Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. Materials and methods HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose–induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting . Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2 , and GSK3β. Results DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong. Conclusions DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
内分泌学
·
糖尿病
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）