Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Plant Physiol Biochem ; 160: 120-129, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33485150

RESUMO

As senescence progresses, the sensitivity of wheat organs to plant hormones during the grain-filling stages cannot be ignored. Especially under water deficit situation, non-leaf organs (spikes) have better photosynthesis and drought-tolerance traits than flag leaves. However, the mechanism of ethylene synthesis in wheat organs under water deficit remains unclear. We have studied the influence of water deficit in wheat flag leaves and spike bracts on photosynthetic parameters and on the expression of key enzymes involved in the ethylene biosynthesis pathway during the late grain-filling stages. More stable chlorophyll content (Chl), maximum PSII quantum yield (Fv/Fm), nonphotochemical quenching (NPQ) and maximal efficiency of PSII photochemistry under light adaptation (Fv'/Fm') were observed in the spike bracts than that in the flag leaves during the late grain-filling stages. In addition, the activity of glutathione reductase (GR), γ-glutamylcysteine synthetase (γ-ECS), 1-aminocyclopropane-1-carboxylic (ACC) acid synthase (ACS), and ACC oxidase (ACO) induced ethylene synthesis and influenced plant growth. Further analysis of genes encoding cysteine-ethylene related proteins (γ-ECS, GR, ACO, ACS1, and ASC2) demonstrated that ear organs and flag leaves exhibited different expression patterns. These findings will facilitate future investigations of the regulatory senescence response mechanisms of cysteine interaction with ethylene in wheat under conditions of drought stress.


Assuntos
Etilenos/biossíntese , Glutationa/biossíntese , Estresse Fisiológico , Triticum/fisiologia , Água/fisiologia , Clorofila , Secas , Fotossíntese , Folhas de Planta
2.
Life Sci ; 270: 119133, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33508298

RESUMO

AIMS: Kaempferide (Ka, 3,5,7-trihydroxy-4'-methoxyflavone), an active ingredient of Tagetes erecta L., has been demonstrated to possess many pharmacological effects, including antioxidant, anti-inflammation, anticancer and antihypertension in previous study. However, there is no evidence of Ka on metabolic disorder in former studies. This study investigated the effects of Ka on glycolipid metabolism and explored the underlying mechanisms of action in vivo and vitro. MATERIALS AND METHODS: The mouse model of glycolipid metabolism disorder was induced by high-fat diet (HFD). The effects of Ka were evaluated on bodyweight, lipid metabolism and glucose metabolism. Hypolipidemic effect was examined by blood sample analysis. The hypoglycemic effect was detected by several indicators, like blood glucose, serum insulin, HOMA index and intraperitoneal glucose tolerance tests (IPGTT). The signaling pathways of lipid metabolism (PPARγ/LXRα/ABCA1) and glucose metabolism (PPARγ/PI3K/AKT) were evaluated using Real-Time PCR and Western blot. The primary culture of hepatocyte was prepared to confirm the target of Ka by co-culturing with PPARγ agonist or inhibitor. KEY FINDINGS: The HFD mice developed obesity, hyperlipidemia, hyperglycemia and insulin resistance. Administration of Ka at a dose of 10 mg/kg.BW for 16 weeks effectively attenuated these changes. Further studies revealed the hypolipidemic and hypoglycemic effects of Ka depended on the activation of PPARγ/LXRα/ABCA1 and PPARγ/PI3K/AKT pathways, respectively. The primary hepatocyte test, co-cultured with PPARγ agonists or inhibitors, further confirmed the above signaling pathway and key protein. SIGNIFICANCE: These results suggested that Ka played an important role in improving glycolipid metabolism disorder. These favorable effects were causally associated with anti-obesity. The underlying mechanisms might have to do with the activation of the PPARγ and its downstream signaling pathway. Our study helped to understand the pharmacological actions of Ka, and played a role for Ka in the effective treatment of obesity, diabetes, nonalcoholic hepatitis and other metabolic diseases.


Assuntos
Quempferóis/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , PPAR gama/metabolismo , Adipócitos/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Glicolipídeos/metabolismo , Hiperlipidemias/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Quempferóis/metabolismo , Fígado/metabolismo , Masculino , Doenças Metabólicas/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , PPAR gama/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
3.
Obes Res Clin Pract ; 14(4): 368-374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32631803

RESUMO

AIMS: Scutellarein (Sc), a natural compound and an active ingredient of Erigeronbrevis-capus (Vant.), shows anti-obesity, anti-inflammation and lipid-lowering properties in our previous study. However, no previous in vivo and vitro has been conducted to assess the effects of Sc in insulin resistance (IR). This study investigated the effects of Sc on IR and oxidative stress and explored the underlying mechanisms of action in vivo and vitro. MATERIAL AND METHOD: A well-established mouse model of IR, induced by high-fat diet (HFD) feeding, was applied in this study. The effects of Sc were evaluated on obesity, glycometabolism disorder and oxidative stress. The anti-IR effect was assessed using blood glucose, serum insulin, HOMA index, intraperitoneal glucose tolerance tests (IPGTT), intraperitoneal insulin tolerance tests (IPITT), and glucose-regulating enzyme activity. The insulin signaling pathways and AMPKα expressions were tested by Western blot. The primary culture of hepatocytes was prepared and used for confirming the above signaling pathways. RESULTS: Obesity, IR and oxidative stress developed in HFD mice. Administration of Sc at a dose of 50mg/kg for 16 weeks effectively attenuated these changes. Further studies revealed the antagonistic effect of Sc on IR was a result of the activation of the insulin signaling pathway and AMPKα. The primary hepatocyte test, stimulated by high glucose, further confirmed that SC exerts anti-IR through the above signaling pathway and key protein. CONCLUSION: These results suggested that Sc possesses not only an important novel anti-IR effect but also an anti-oxidative stress effect. These favorable effects were causally associated with weight loss and the improved glycometabolism. The underlying mechanisms might associated with the activation of the insulin signaling pathway and AMPKα. Our study promotes the understanding of the pharmacological actions of Sc, and plays a role for Sc in the effective treatment of diabetes mellitus.

4.
Ecotoxicol Environ Saf ; 194: 110402, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151867

RESUMO

Sulfur (S) application in pakchoi (Brassica chinensis L.) cultivation is vital for reducing cadmium (Cd) accumulation in the plants. However, the mechanism of S application on Cd uptake and translocation in pakchoi is unclear. In this study, a hydroponic experiment was performed to investigate the effects of S application on Cd accumulation in pakchoi at one Cd concentration (50 µM, in comparison to the control condition, 0 µM) and three S levels (0, 2, 4 mM). The results showed that excessive S application (4 mM) reduced Cd accumulation and alleviated pakchoi growth inhibition caused by Cd stress in shoots and roots. With increased S application, the proportion of Cd in the vacuolar fraction and the proportion of NaCl-extractable Cd increased in roots. Additionally, S application increased the content of glutathione (GSH) and phytochelatins (PCs). The reduced Cd uptake and accumulation in pakchoi shoots could have been due to increased Cd chelation and vacuolar sequestration in roots. In addition, sufficient S application (2 mM) increased the expression of γ-glutamylcysteine synthetase (GSH1) and nicotinamide synthase (NAS) in roots, and excessive S application upregulated the expression of ATP sulfurylase (ATPS) and phytochelatin synthase (PCs). This study provides evidence for the mechanism of mitigating Cd toxicity in pakchoi and will be helpful for developing strategies to reduce Cd accumulation in the edible parts of pakchoi through S fertilizer application.


Assuntos
Brassica/efeitos dos fármacos , Cádmio/metabolismo , Poluentes do Solo/metabolismo , Sulfatos/farmacologia , Aminoaciltransferases/metabolismo , Transporte Biológico , Brassica/crescimento & desenvolvimento , Brassica/metabolismo , Cádmio/toxicidade , Fertilizantes/análise , Glutationa/metabolismo , Hidroponia , Modelos Teóricos , Fitoquelatinas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Poluentes do Solo/toxicidade , Sulfato Adenililtransferase/metabolismo , Sulfatos/metabolismo
5.
J Exp Zool A Ecol Integr Physiol ; 333(4): 240-251, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31994847

RESUMO

Ecological immunology involves the study of the immune function of wildlife, which is seldom compared with that of model animals. Here, we evaluated and compared the level of the innate immune response in the plateau zokor (Eospalax baileyi), an indigenous underground rodent from the Tibetan Plateau, with that in the bamboo rat (Rhizomys pruinosus) and Sprague-Dawley (SD) rat (Rattus norvegicus). The spleen was observed by ordinary light and transmission electron microscopy, and the spleen index was calculated. After liposaccharide (LPS) challenge, the expression of Toll-like receptor 2 (TLR2), TLR4, and hypoxia-inducible factor 1α (HIF-1α) in the spleen was detected by Western blot analysis and immunofluorescence. The expression of nuclear factor-κB1 (NF-κB1) and mitogen-activated protein kinase 14 (MAPK14) in the spleen was detected by real-time quantitative polymerase chain reaction, and the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-ß (IFN-ß) in the spleen were detected by enzyme-linked immunoassay. The spleen index of the plateau zokor was lower than that of the bamboo rat and SD rat. The expression of TLR4, NF-κB1, and MAPK14 and the levels of IL-6 and TNF-α in the spleen of the plateau zokor were lower than those of the bamboo rat and SD rat, while the expression of TLR2 and HIF-1α and the level of IFN-ß were higher than those of the bamboo rat and SD rat. We speculate that suppression of the TLR4 signaling pathway in the plateau zokor is an adaptation to hypoxic tunnels that decreases antigenic risk and maintains immune homeostasis. Moreover, the spleen of the plateau zokor is reduced in size, reducing the innate immunity investment in the spleen. We also noted that high levels of HIF-1α in the spleen of the plateau zokor suppressed crosstalk between HIF-1α and TLR4, promoting the innate immune response.

6.
Am J Physiol Regul Integr Comp Physiol ; 317(5): R696-R708, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31508994

RESUMO

The plateau zokor (Eospalax baileyi) is a species of subterranean rodent endemic to the Tibetan Plateau. It is well adapted to the cold and hypoxic and hypercapnic burrow. To study the oxygenation properties of plateau zokor hemoglobins (Hbs), we measured intrinsic Hb-O2 affinities and their sensitivities to pH (Bohr effect); CO2; Cl-, 2,3-diphosphoglycerate (DPG); and temperature using purified Hbs from zokor and mouse. The optimal deoxyHb model of plateau zokor was constructed and used to study its structural characteristics by molecular dynamics simulations. O2 binding results revealed that plateau zokor Hbs exhibit remarkably high intrinsic Hb-O2 affinity, low CO2 effects compared with human and the relatively low anion allosteric effector sensitivities (DPG and Cl-) at normal temperature, which would safeguard the pulmonary Hb-O2 loading under hypoxic and hypercapnic conditions. Furthermore, the high anion allosteric effector sensitivities at low temperature and low temperature sensitivities of plateau zokor Hbs would facilitate the releasing of O2 in cold extremities and metabolic tissues. However, the high Hb-O2 affinity of plateau zokor is not compensated by high pH sensitivity as the Bohr factors of plateau zokor Hbs were as low as those of mouse. The results of molecular dynamics simulations revealed the reduced hydrogen bonding between the α1ß1- and α2ß2-dimer interface of deoxyHb in zokor compared with mouse. It may be the primary mechanism of the high intrinsic Hb-O2 affinities in zokor. Specifically, substitution of the 131Ser→Asn in the α2-chain weakened the connection between α1- and ß2-subunit.


Assuntos
Hemoglobinas/metabolismo , Consumo de Oxigênio , Oxigênio/sangue , Oxiemoglobinas/metabolismo , Animais , Biomarcadores/sangue , Temperatura Corporal , Dióxido de Carbono/sangue , Hemoglobinas/química , Humanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Simulação de Dinâmica Molecular , Oxiemoglobinas/química , Ligação Proteica , Estrutura Terciária de Proteína , Subunidades Proteicas , Roedores , Especificidade da Espécie , Relação Estrutura-Atividade
7.
Plant Physiol Biochem ; 142: 163-172, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31299598

RESUMO

C4 photosynthetic enzymes are present in C3 plants and participate in non-photosynthetic metabolism. Wheat spike bracts had a higher drought tolerance, photosynthesis and senesced later compared to the flag leaves under water deficit. This research was conducted to investigate the different response of primary carbon metabolism induced by C4 photosynthetic enzymes in wheat flag leaves and spike bracts including glumes and lemmas under water deficit. The activities of C4 photosynthetic enzymes and Ribulose bisphosphate carboxylase oxygenase (Rubisco), the expression of related genes and primary carbon metabolism contents were demonstrated in wheat flag leaves and spike bracts exposed to water deficit. Results showed that drought stress strongly inhibited wheat photosynthetic metabolism by decreasing Rubisco activity in flag leaves. The activities of phosphoenolpyruvate carboxylase (PEPC), NADP-malic enzyme (NADP-ME), phosphate dikinase (PPDK) and NADP- malic dehydrogenase (NADP-MDH) increased in wheat spike bracts under water deficit. Transcript levels of C4 photosynthetic genes in wheat spike bracts were higher under water deficit than that of control. Furthermore, the results indicated that drought stress induced changes in the contents of primary carbon metabolism including malate, oxaloacetic acid (OAA), citric, fumaric acid were organ-specific. In conclusion, the functions of C4 photosynthetic enzymes appear to be important for wheat spike bracts primary carbon metabolism and defence response under drought stress.


Assuntos
Carbono/metabolismo , Enzimas/genética , Enzimas/metabolismo , Triticum/fisiologia , Mapeamento Cromossômico , Cromossomos de Plantas , Secas , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Fosfoenolpiruvato Carboxilase/genética , Fosfoenolpiruvato Carboxilase/metabolismo , Fotossíntese/genética , Filogenia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ribulose-Bifosfato Carboxilase/genética , Ribulose-Bifosfato Carboxilase/metabolismo , Triticum/metabolismo
8.
Biomed Pharmacother ; 117: 109042, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228804

RESUMO

AIMS: Scutellarein (Sc), a natural compound and an active ingredient of Erigeron breviscapus (vant.), shows anti-inflammatory and antioxidant properties and has the potential for obesity treatment. However, no previous in vivo study has been conducted to assess the role of Sc in obesity. This study investigated the effects of Sc on obesity and associated hyperlipidemia and fatty liver and explores the underlying mechanisms of action in a mouse model. METHODS: The study was conducted using a well-established mouse model of obesity induced by high-fat diet (HFD) feeding. Anti-obesity effects were assessed using body weight, abdominal circumference, white adipose tissue, adiposity index, and fatty liver index. Lipid lowering and liver protective effects were examined by blood sample analysis. Lipid dystopia deposition was confirmed by liver pathological sections. The signaling pathways of lipid metabolism and cytokine/inflammatory mediator were evaluated using Real-Time PCR and Western blot. RESULTS: Central obesity, dyslipidemia, inflammation, and hepatic steatosis were developed in mice fed with HFD. Administration of Sc at a dose of 50 mg/kg for 16 weeks effectively attenuated all obesity indicators tested. Further studies revealed the antagonistic effect of Sc on hyperlipidemia was a result of the repression of the lipid synthesis pathway, de novo pathway, HMGCR, promoting fatty acid oxidation (PPARα, CPT-1a) and increased cholesterol output (PPARγ-LXRα-ABCA1). The anti-inflammatory effect was attributed to blocking the expression of inflammatory genes, including TNF-α, IL-6, NF-κB. CONCLUSIONS: These results suggest that Sc possesses important novel anti-obesity effects accompanying lipid lowering and anti-inflammation-based liver protective effects. These favorable effects are causally associated with the suppression of gene expression of inflammatory cytokines and fine regulation of genes responsible for energy metabolism. Our results advance the understanding of the pharmacological actions of Sc, and provides a role for Sc in effective management of obesity.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Apigenina/uso terapêutico , Obesidade/tratamento farmacológico , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Apigenina/química , Apigenina/farmacologia , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Dieta Hiperlipídica , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/complicações , Hiperlipidemias/fisiopatologia , Inflamação/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/genética , Obesidade/fisiopatologia , Tamanho do Órgão/efeitos dos fármacos
9.
Mol Med Rep ; 20(2): 931-938, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173254

RESUMO

Vascular remodeling induced by long­term hyperglycaemia is the main pathological process in diabetic vascular complications. Thus, vascular remodeling may be a potential therapeutic target in diabetes mellitus (DM) with macrovascular disease. The present study aimed to investigate the effect of RING finger protein 10 (RNF10) on vascular remodeling under conditions of chronic hyperglycaemia stimulation. We found that overexpression of RNF10 clearly decreased intimal thickness and attenuated vascular remodeling in DM. TUNEL staining showed that apoptosis was clearly inhibited, an effect that may be mediated by decreases in Bcl­2 protein expression. Quantitative analysis demonstrated that overexpression of RNF10 could suppress inflammation by reducing the levels of TNF­α, and MCP­1 mRNA and NF­κB protein. Meanwhile, overexpression of RNF10 prevented vascular smooth muscle cell (VSMC) hyperproliferation through the downregulation of cyclin D1 and CDK4 proteins. Notably, short hairpin RNF10 (shRNF10) greatly aggravated the pathological responses of diabetic vascular remodeling. These outcomes revealed that the differential expression of RNF10 had a completely opposite effect on vascular damage under hyperglycaemia, further displaying the core function of RNF10 in regulating vascular remodeling induced by diabetes. Consequently, RNF10 could be a novel target for the treatment of diabetic vascular complications.


Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus Experimental/genética , Angiopatias Diabéticas/genética , Hiperglicemia/genética , Miócitos de Músculo Liso/metabolismo , Proteínas do Tecido Nervoso/genética , Animais , Apoptose/genética , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Resistência à Insulina/genética , Masculino , Miócitos de Músculo Liso/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
IUBMB Life ; 71(5): 632-642, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30597731

RESUMO

Vascular smooth muscle cell (VSMC) hyperproliferation is the main pathological process in various cardiovascular diseases, such as vascular restenosis. This process may be repressed by RING finger protein 10 (RNF10) in metabolic syndrome (MetS) rats. The aim of this study is to evaluate the inhibitory effects and molecular mechanisms of RNF10 on VSMC hyperproliferation. Neointimal hyperplasia in MetS and high-glucose-induced VSMC hyperproliferation were measured after infection with adenoviruses encoding RNF10 (Ad-RNF10), short hairpin RNF10 (Ad-shRNF10), or green fluorescent protein (Ad-GFP). In vivo and in vitro, we found that overexpression of RNF10 significantly affected neointima formation and VSMC proliferation, and displayed further inhibitory activity by promoting mesenchyme homeobox 2 (Meox2) and suppressing activating protein 1 (AP-1). In contrast, Ad-shRNF10 had an opposite effect on neointimal hyperplasia and VSMC hyperproliferation in vivo and in vitro. Our study indicated that RNF10 inhibited the hyperproliferation with the activities of Meox2 and AP-1 proteins. RNF10 may be a next drug target for treating vascular restenosis and other related cardiovascular diseases. © 2018 IUBMB Life, 71(5):632-642, 2019.


Assuntos
Proteínas de Transporte/metabolismo , Proliferação de Células , Reestenose Coronária/prevenção & controle , Hiperplasia/prevenção & controle , Síndrome Metabólica/fisiopatologia , Músculo Liso Vascular/citologia , Neointima , Proteínas do Tecido Nervoso/metabolismo , Adenoviridae/fisiologia , Infecções por Adenoviridae/virologia , Angioplastia Coronária com Balão/efeitos adversos , Animais , Proteínas de Transporte/genética , Movimento Celular , Células Cultivadas , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Dieta Hiperlipídica/efeitos adversos , Hiperplasia/etiologia , Hiperplasia/patologia , Masculino , Síndrome Metabólica/etiologia , Músculo Liso Vascular/metabolismo , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
11.
Life Sci ; 208: 325-332, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29723537

RESUMO

AIMS: Vascular restenosis and neointimal hyperplasia are enhanced in metabolic syndrome (MetS). Vascular smooth muscle cell (VSMC) proliferation is a key step during restenosis and is suppressed by RING finger protein 10 (RNF10). However, the effect of RNF10 on neointimal hyperplasia is unknown. In the present study, we explored whether RNF10 over-expression prevents neointimal hyperplasia in a MetS rat model and in cultured VSMCs exposed to high glucose. MAIN METHODS: An adenovirus encoding RNF10 (Ad-RNF10) or control green fluorescent protein (Ad-GFP) was delivered to balloon-injured carotid arteries in MetS rats and cultured rat VSMCs exposed to high glucose. Neointimal hyperplasia was measured, and the apoptosis index in the neointima was evaluated. The protein levels of RNF10, caspase-3, Bcl-2 and Bax in the injured vessels and VSMCs were determined. KEY FINDINGS: Ad-RNF10 prevented the development of neointimal hyperplasia in balloon-injured vessels. Furthermore, an increase in the apoptosis index and cleaved caspase-3 protein expression and a decrease in Bcl-2 expression were detected in the injured vessels after Ad-RNF10 treatment. Meanwhile, increased caspase-3 protein expression and decreased Bcl-2 expression were detected in VSMCs treated with Ad-RNF10. SIGNIFICANCE: RNF10 over-expression strongly suppresses neointimal hyperplasia via increased apoptosis, constituting a promising new therapeutic target for vascular restenosis.


Assuntos
Apoptose , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Hiperplasia/patologia , Síndrome Metabólica/fisiopatologia , Músculo Liso Vascular/patologia , Neointima/patologia , Proteínas do Tecido Nervoso/metabolismo , Animais , Proteínas de Transporte/genética , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Hiperplasia/etiologia , Hiperplasia/metabolismo , Técnicas In Vitro , Masculino , Síndrome Metabólica/etiologia , Músculo Liso Vascular/metabolismo , Neointima/etiologia , Neointima/metabolismo , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
12.
Zhongguo Zhong Yao Za Zhi ; 41(17): 3290-3295, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-28920385

RESUMO

To explore the effects of hesperidin on glycolipid metabolic disorders and its mechanism in mice induced by high-fat diet, 40 male C57 mice were randomly divided into control group, OB group, low dose group (OB+ hes-low) and high dose group (OB+ hes-high) according to the diet. After 16 weeks, the body weight, liver index and visceral fat index in all mice were detected. The glucose metabolism indications (blood glucose, insulin levels and HOMA-IR) and serum lipid levels were evaluated. The mRNA expression of insulin signaling pathway genes(IR, IRS1, Glut2, Glut4), lipid metabolism pathway genes(SREBP-1c, FAS, ACC, PPARα) and AMPK were analyzed by Real-time PCR. After 16-week feeding, the indicators in OB group were higher than those in control group, including body weight, body fat deposition, serum glucose, serum lipid, serum insulin and HOMA-IR index (P<0.05). And impaired glucose tolerance occurred in the OB group (P<0.05). Treating with hesperidin, whether in low or high dose, attenuated these changes (P<0.05), especially in high dose group(P<0.05). Hesperidin, especially in high dose, upregulated the mRNA expressions of AMPK (P<0.05), which had impact on the gene expressions of insulin signaling pathway (IR, IRS-1, Glut2/4) (P<0.05) and lipid metabolism related genes (SREBP-1c and Fas and ACC) (P<0.05). The activatory effect of hesperidin on the mRNA expressions of PPARα was also observed (P<0.05), especially in high dose group (P<0.05). Hesperidin inhibits obesity, hyperglycemia, hyperlipemia and attenuates insulin resistance. These effects might be closed related to the activation of AMPK, which regulate the insulin signaling pathway and lipid metabolism.


Assuntos
Hesperidina/farmacologia , Resistência à Insulina , Animais , Glicemia/análise , Dieta Hiperlipídica , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Insulina/sangue , Metabolismo dos Lipídeos , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Transdução de Sinais
13.
Cell Physiol Biochem ; 33(4): 1176-85, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24752040

RESUMO

BACKGROUND: Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R) injury under diabetic condition has not been evaluated. METHODS: To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis. RESULTS: Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-κB. CONCLUSION: Overexpression of Suv39h1 results in the de-activation of proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore, Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under diabetic condition.


Assuntos
Metiltransferases/metabolismo , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteínas Repressoras/metabolismo , Adenoviridae/genética , Animais , Apoptose , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Vetores Genéticos/metabolismo , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos/patologia , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Regulação para Cima
14.
Zhongguo Zhong Yao Za Zhi ; 38(9): 1378-85, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-23944073

RESUMO

Eighteen compounds were isolated by a combination of various chromatographic techniques including column chromatography over macroporous resin, MCI gel, silica gel, and sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by spectroscopic data analysis as adinoside A (1), stryspinoside (2), benzyl alcohol beta-glucopyranoside (3), benzyl 2-o-beta-D-glucopyranosyl-2,6-dihydroxybenzoate (4) , gentisic acid 2-O-beta-D-glucopyranoside (5), eugenyl beta-D-glucopyranoside (6) , eugenyl-P-xylopyranosyl-(1-->6)-beta-glucopyranoside (7), (-)-lyoniresinol 9-O-fP-D-glucopyranoside (8) , (+)-lyoniresinol 9-O-beta-D-glucopyranoside (9) , apigenin-7-O-L-rhamnopyranoside (10), luteolin-3 '-O-L-rhamnoside (11) , ursolic acid (12) , beta-sitosteryl-3beta-glucopyranoside-6'-O-palmitate (13), abscisic acid (14), guanosine (15), 5-methyluracil (16), trans-cinnamic acid (17), and 4-hydroxybenzaldehyde(18). These compounds were obtained from this plant for the first time.


Assuntos
Flores/química , Lonicera/química , Benzaldeídos/análise , Gentisatos/análise , Glucosídeos/análise , Hidroxibenzoatos/análise , Luteolina/análise , Timina/análise , Triterpenos/análise
15.
Saudi Med J ; 34(7): 719-26, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23860892

RESUMO

OBJECTIVE: To evaluate the prognostic value of late gadolinium enhancement (LGE) in dilated cardiomyopathy (DCM) patients. METHODS: We searched PubMed, MEDLINE, the Cochrane library and EMBASE databases from September to December 2012 in the Renmin Hospital of Wuhan University, Wuhan, China for studies of LGE in DCM patients. We extracted the clinical outcomes (all-cause mortality, cardiovascular mortality, sudden cardiac death [SCD], aborted SCD, heart failure hospitalization) after carefully reviewed. A meta-analysis was performed to calculate pooled odds ratios (OR) with 95% confidence intervals (CIs) for prognostic outcomes in LGE positive versus LGE negative patients with DCM. RESULTS: Five studies for 545 DCM patients were contained in this meta-analysis. The results showed LGE positive patients was significantly associated with higher cardiovascular mortality (pooled OR: 2.67; 95% CI: 1.12-6.35; p=0.03), aborted SCD (pooled OR: 5.26; 95% CI: 1.57-17.55; p=0.007), and heart failure hospitalization (pooled OR: 3.91; 95% CI: 1.99-7.69; p<0.001). CONCLUSION: Late gadolinium enhancement during cardiac MRI is significantly associated with cardiovascular mortality, aborted SCD and heart failure hospitalization in DCM patients. The LGE can be a potential stratification tool to predict the risk of cardiac events among patients with DCM.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/mortalidade , Meios de Contraste , Morte Súbita Cardíaca/etiologia , Gadolínio , Cardiomiopatia Dilatada/complicações , Humanos , Imagem por Ressonância Magnética , Valor Preditivo dos Testes , Fatores de Tempo
16.
J Mol Histol ; 44(5): 575-85, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23719775

RESUMO

Cardiac remodelling is a major determinant of heart failure (HF) and is characterised by cardiac hypertrophy, fibrosis, oxidative stress and myocytes apoptosis. Hesperetin, which belongs to the flavonoid subgroup of citrus flavonoids, is the main flavonoid in oranges and possesses multiple pharmacological properties. However, its role in cardiac remodelling remains unknown. We determined the effect of hesperetin on cardiac hypertrophy, fibrosis and heart function using an aortic banding (AB) mouse. Male, 8-10-week-old, wild-type C57 mice with or without oral hesperetin administration were subjected to AB or a sham operation. Our data demonstrated that hesperetin protected against cardiac hypertrophy, fibrosis and dysfunction induced by AB, as assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. Also, hesperetin attenuated oxidative stress and myocytes apoptosis induced by AB. The inhibitory effect of hesperetin on cardiac remodelling was mediated by blocking PKCα/ßII-AKT, JNK and TGFß1-Smad signalling pathways. In conclusion, we found that the orange flavonoid hesperetin protected against cardiac remodelling induced by pressure overload via inhibiting cardiac hypertrophy, fibrosis, oxidative stress and myocytes apoptosis. These findings suggest a potential therapeutic drug for cardiac remodelling and HF.


Assuntos
Cardiomegalia/prevenção & controle , Cardiotônicos/farmacologia , Coração/efeitos dos fármacos , Hesperidina/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Cardiomegalia/genética , Cardiomegalia/patologia , Fibrose , Regulação da Expressão Gênica , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteína Quinase C beta/genética , Proteína Quinase C beta/metabolismo , Proteína Quinase C-alfa , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteínas Smad/genética , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Pressão Ventricular
17.
Cell Physiol Biochem ; 31(2-3): 230-41, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23428596

RESUMO

BACKGROUND/AIM: Oxidative stress plays a critical role in pathogenesis of the neointimal arterial hyperplasia. The aim of the study was to evaluate effects of resveratrol (RSV) on the vascular hyperplasia stimulated by oxidative damage. METHODS: Balloon vascular injury was induced in rats that were intraperitonealy exposed to resveratrol (1 mg/kg) on 7 or 14 days after surgical procedure. Animals were euthanized on 7 or 14 days after operation. The blood level of 8-iso-prostaglandin F2α, arterial morphology as well as expression of monocyte chemotactic protein-1 and interleukin-6 in carotid wall were measured. Vascular smooth muscle cells (VSMCs) were isolated from the thoracic aorta. Cellular proliferation and migration assays, reactive oxygen species (ROS), superoxide dismutase (SOD) and NADPH oxidative activity, protein level of ß-actin, histone H3, NF-ĸB p65, IĸB, ERK1/2, phospho-ERK1/2, phospho-p38 as well as NF-ĸB transcription activity were evaluated in-vitro after angiotensin II stimulation and resveratrol (50-200 µmol/L) treatment. RESULTS: Significant decreases in neointimal/medial area, serum prostaglandin level and genes expression were found in rats treated with resveratrol, when compared to the control group. Significant changes were also revealed for proliferation and migration rates, ROS level, as well as SOD, NADPH oxidase, ERK1/2 phosphorylation and NF-ĸB transcriptional activity in cell cultures exposed to highest dose of resveratrol. Insignificant changes were observed for NF-kappaB p65 translocation and IĸB degradation, p38 phosphorylation in MAPK pathway. CONCLUSION: Resveratrol significantly suppressed the neointimal hyperplasia after balloon injury through inhibition of oxidative stress and inflammation by blocking the ERK1/2/NF-kappa B pathway.


Assuntos
Antioxidantes/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Aorta Torácica/citologia , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Modelos Animais de Doenças , Interleucina-6/metabolismo , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , NADPH Oxidases/metabolismo , NF-kappa B/genética , Fosforilação , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Transcrição Genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Mol Cell Endocrinol ; 362(1-2): 128-38, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22698522

RESUMO

The aim of the present study was to determine the effect of baicalein on metabolic syndrome induced by a high-fat diet in mice. The mice developed obesity, dyslipidemia, fatty liver, diabetes and insulin resistance. These disorders were effectively normalized in baicalein-treated mice. Further investigation revealed that the inhibitory effect on inflammation and insulin resistance was mediated by inhibition of the MAPKs pathway and activation of the IRS1/PI3K/Akt pathway. The lipid-lowering effect was attributed to the blocking of synthesis way mediated by SERBP-1c, PPARγ and the increased fatty acid oxidation. All of these effects depended on AMPKα activation. These results were confirmed in the primary hepatocytes from wild type and AMPKα(2)(-/-) mice. However, the IRS-1/PI3K/AKT pathway showed no change, which may be due to the time of stimulation and concentration. Thus, these data suggested that baicalein protects mice from metabolic syndrome through an AMPKα(2)-dependent mechanism involving multiple intracellular signaling pathways.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Ativadores de Enzimas/farmacologia , Flavanonas/farmacologia , Síndrome Metabólica/tratamento farmacológico , Animais , Vias Biossintéticas/genética , Glicemia , Peso Corporal/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/sangue , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolismo Energético , Ativadores de Enzimas/uso terapêutico , Ácidos Graxos/biossíntese , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Flavanonas/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Resistência à Insulina , Sistema de Sinalização das MAP Quinases , Masculino , Síndrome Metabólica/enzimologia , Síndrome Metabólica/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Obesidade Abdominal/tratamento farmacológico , Obesidade Abdominal/enzimologia , Obesidade Abdominal/etiologia , Estresse Oxidativo , Fator de Necrose Tumoral alfa/sangue
19.
Arch Biochem Biophys ; 518(1): 61-70, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22198281

RESUMO

Metabolic syndrome is a low-grade inflammatory state in which oxidative stress is involved. Naringin, isolated from the Citrussinensis, is a phenolic compound with anti-oxidative and anti-inflammatory activities. The aim of this study was to explore the effects of naringin on metabolic syndrome in mice. The animal models, induced by high-fat diet in C57BL/6 mice, developed obesity, dyslipidemia, fatty liver, liver dysfunction and insulin resistance. These changes were attenuated by naringin. Further investigations revealed that the inhibitory effect on inflammation and insulin resistance was mediated by blocking activation of the MAPKs pathways and by activating IRS1; the lipid-lowering effect was attributed to inhibiting the synthesis way and increasing fatty acid oxidation; the hypoglycemic effect was due to the regulation of PEPCK and G6pase. The anti-oxidative stress of naringin also participated in the improvement of insulin resistance and lipogenesis. All of these depended on the AMPK activation. To confirm the results of the animal experiment, we tested primary hepatocytes exposed to high glucose system. Naringin was protective by phosphorylating AMPKα and IRS1. Taken together, these results suggested that naringin protected mice exposed to a high-fat diet from metabolic syndrome through an AMPK-dependent mechanism involving multiple types of intracellular signaling and reduction of oxidative damage.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica/efeitos adversos , Flavanonas/farmacologia , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Ativação Enzimática/efeitos dos fármacos , Flavanonas/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Gluconeogênese/genética , Glucose/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...