Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Cell Death Dis ; 11(5): 386, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439850

RESUMO

Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character in pancreatic cancer remains unclear. The expression of HJURP was assessed in PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient or overexpressed PDAC cell lines were constructed, using shRNA or plasmids with HJURP insert. MTT, sphere formation assay, migration, and invasion assays were performed to evaluate the viability, proliferation, migration, and invasion of PDAC cells. We used xenograft mice models to assess the tumor growth and metastasis in vivo. RNA-seq was applicated in search of the potential downstream target of HJURP in PDAC and subsequent verification were fulfilled via multiple assays, including immunofluorescence. Additionally, chromatin immunoprecipitation and luciferase reporter assay were conducted to explore the potential regulation of MDM2 expression by HJURP through H3K4me2. In this current research, we found that the expression of HJURP in PDAC cells and tissue was significantly higher than those of adjacent normal tissue, and high HJURP expression predicted poor survival. HJURP significantly promoted the viability, sphere formation, migration, and invasion of PDAC cells in vitro, HJURP also facilitated tumor growth and metastasis in vivo. Mechanically, MDM2/p53 axis is critical for HJURP-mediated malignant behaviors in PDAC, and HJURP regulates MDM2 expression through H3K4me2. HJURP could serve as a promising biomarker, and target for PDAC prognosis and treatment.

2.
Cancer Med ; 8(9): 4159-4168, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31197975

RESUMO

Eukaryotic initiation factor 3 (EIF3) is one of the largest and most complex translation initiation factors, which consists of 13 subunits named eukaryotic translation initiation factor 3 subunit A (EIF3a) to EIF3m. EIF3a is the largest subunit of EIF3. Previous studies suggested that EIF3a is a housekeeping gene, recent results have found that EIF3a is closely related to the tumorigenesis and drug resistance. Circular RNAs (circRNAs) derived from biologically important gene can play an important role in gene regulation. However, the mechanism underlying circRNAs' biological functions is not well understood yet. In this work, we screened 31 EIF3a-derived circRNAs, in which two circEIF3as were identified to be correlated with cisplatin drug sensitivity in lung cancer. Two circEIF3as were found involved in RNA-binding proteins-mediated biological processes and may be related to translational regulation according to bioinformatics analyses. CircEIF3as, the transcriptional initiation factor EIF3a transcribed circRNAs, are associated with both drug sensitivity and translation regulation. These findings mean that they may have a functional synergy effect with EIF3a or be valuable therapeutic targets for treatment like EIF3a. This is the first study that exploits circRNAs screening from EIF3a in lung cancer, our findings provide a novel perspective on the function of EIF3a and circEIF3as in lung cancer.

3.
Oncotarget ; 7(51): 85235-85243, 2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27835911

RESUMO

Lung cancer remains as the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. This study aims to investigate biomarkers associated with cancer progression and prognosis of LUAD. We integrated expression profiles of 668 lung cancer patients in five datasets from the Gene Expression Omnibus (GEO) and identified a panel of differentially expressed genes (DEGs). Function enrichment analysis highlighted that these genes were closely associated with the carcinogenesis of LUAD, such as cell cycle, ECM-receptor interaction and p53 signaling pathway. Cyclin-dependent kinase 1 (CDK1) and MAD2 mitotic arrest deficient-like 1 (MAD2L1), two critical mitotic checkpoint genes, were selected for further study. Elevated expression of CDK1 and MAD2L1 was validated in an independent LUAD cohort. Kaplan-Meier analysis revealed that CDK1 and MAD2L1 expression was negatively correlated with both overall survival (OS) and relapse-free survival (RFS). In conclusion, CDK1 and MAD2L1 were adverse prognostic biomarkers for LUAD whose increased expression could render patients with LUAD a high risk of cancer recurrence and poor survival, suggesting that they might be applied as potential targets for LUAD treatment.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Proteína Quinase CDC2/metabolismo , Neoplasias Pulmonares/diagnóstico , Proteínas Mad2/metabolismo , Adenocarcinoma/mortalidade , Idoso , Biomarcadores Tumorais/genética , Proteína Quinase CDC2/genética , Carcinogênese , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Proteínas Mad2/genética , Masculino , Mitose/genética , Valor Preditivo dos Testes , Prognóstico , Transdução de Sinais , Análise de Sobrevida , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
4.
Int J Mol Sci ; 17(6)2016 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-27258253

RESUMO

Lung cancer is the leading cause of cancer death worldwide due to its high incidence and mortality. As the most common lung cancer, non-small cell lung cancer (NSCLC) is a terrible threat to human health. Despite improvements in diagnosis and combined treatments including surgical resection, radiotherapy and chemotherapy, the overall survival for NSCLC patients still remains poor. DNA damage is considered to be the primary cause of lung cancer development and is normally recognized and repaired by the intrinsic DNA damage response machinery. The role of DNA repair pathways in radio(chemo)therapy-resistant cancers has become an area of significant interest in the clinical setting. Meanwhile, some studies have proved that genetic and epigenetic factors can alter the DNA damage response and repair, which results in changes of the radiation and chemotherapy curative effect in NSCLC. In this review, we focus on the effect of genetic polymorphisms and epigenetic factors such as miRNA regulation and lncRNA regulation participating in DNA damage repair in response to radio(chemo)therapy in NSCLC. These may provide novel information on the radio(chemo)therapy of NSCLC based on the individual DNA damage response.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Reparo do DNA , Epigênese Genética , Neoplasias Pulmonares/terapia , Polimorfismo Genético , Carcinoma Pulmonar de Células não Pequenas/genética , Quimiorradioterapia , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/genética , RNA Longo não Codificante , Resultado do Tratamento
5.
Biomed Pharmacother ; 69: 345-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25661380

RESUMO

l-Carnitine (LC) has protective effects on high glucose-induced oxidative stress in the retinal ganglion cells (RGCs). The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2), Kelch like-ECH-associated protein 1 (Keap1), haemoxygenase-1 (HO-1) and γ-glutamyl cysteine synthetase (γ-GCS) in the protective effect of LC on RGCs. RGCs were first processed with high concentrations of glucose. LC treatment at three concentrations (50µM, 100µM and 200µM) was applied to high glucose stimulated RGCs. The expression of Nrf2, Keap1, haemoxygenase-1 (HO-1) and γ-glutamyl cysteine synthetase (γ-GCS) was quantified by Western blot in the treatment and control (high glucose stimulation) groups. In the three LC groups (50µM, 100µM and 200µM), Nrf-2 (0.71±0.04, 0.89±0.05, 1.24±0.05 vs 0.56±0.03, p<0.05), HO-1 (0.58±0.04, 0.76±0.06, 0.89±0.07 vs 0.25±0.03, p<0.01), and γ-GCS protein expression (0.66±0.03, 0.79±0.05, 0.84±0.08 vs 0.84±0.08, p<0.01) was higher than in the control group. The levels of Keap1 protein were in the LC groups were lower than in the control group (0.50±0.03, 0.45±0.02, 0.53±0.03 vs 0.86±0.05, p<0.01). In conclusion, in high glucose stimulated RGCs, LC treatment was associated with an increased level of Nrf2, HO-1and γ-GCS. LC treatment was also associated with a reduced expression of Keap1 protein. These results suggest that the protective effect of LC treatment on RGCs may be related to Nrf2-Keap1 pathway.


Assuntos
Carnitina/farmacologia , Glucose/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Animais , Forma Celular/efeitos dos fármacos , Glutamato-Cisteína Ligase/metabolismo , Heme Oxigenase-1 , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Ratos Wistar , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/enzimologia
6.
Cancer Cell Int ; 14(1): 141, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25530717

RESUMO

BACKGROUND: H2AX is phosphorylated (γH2AX) by members of the phosphatidylinositol 3-kinase (PI3K) family, including Ataxia telangiectasia-mutated (ATM), ATM- and Rad3-related (ATR) and DNA-PK in response to DNA damage. Our study shows that gossypol acetic acid (GAA) alone can induce γH2AX in Human mucoepidermoid carcinoma cell line (MEC-1) in vitro. Thus, we further examined the possible mechanisms of GAA to induce γH2AX in tumor cells. MATERIALS AND METHODS: The PI3K inhibitors caffeine and wortmannin were used in an effort to identify the kinase(s) responsible for GAA -induced γH2AX in MEC-1 cells. DNA dependent protein kinase (DNA-PK) - proficient and -deficient cells, human glioma cell lines M059K and M059J, were also used to evaluate the kinases responsible for GAA induced H2AX phosphorylation. γH2AX expression was detected by immunofluorescent microscopy. Flow cytometry assay was used to assay γH2AX and cell cycle. RESULTS: GAA induced H2AX phosphorylation in a cell cycle-dependent manner and a significant G0/G1 phase arrest in MEC-1 cells was shown. Caffeine and wortmannin significantly inhibited GAA-induced H2AX phosphorylation in MEC-1 cells. GAA induced H2AX phosphorylation in M059K, but not in M059J. Taken together, these data suggested that GAA treatment alone could induce H2AX phosphorylation in a cell cycle dependent manner in MEC-1 and M059K, but not in M059J cells. A significant G0/G1 phase arrest was shown in MEC-1. CONCLUSIONS: The member of PI3K family, DNA-PK, ATM and ATR are involved in the H2AX phosphorylation of MEC-1 cells.

7.
Braz. j. pharm. sci ; 49(1): 185-191, Jan.-Mar. 2013. graf, tab
Artigo em Inglês | LILACS | ID: lil-671414

RESUMO

The urine excretion of L-carnitine (LC), acetyl-L-carnitine (ALC) and propionyl-Lcarnitine (PLC) and their relations with the antioxidant activities are presently unknown. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Urine concentrations of LC, ALC and PLC were detected by HPLC. Superoxide dismutase (SOD), total antioxidative capacity (T-AOC), malondialdehyde (MDA) and nitrogen monoxidum (NO) activities were measured by spectrophotometric methods. The 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excretion of LC was 53.13±31.36 µmol, 166.93±76.87 µmol, 219.92±76.30 µmol, 100.48±23.89 µmol, 72.07±25.77 µmol, respectively. The excretion of ALC was 29.70±14.43 µmol, 80.59±32.70 µmol, 109.85±49.21 µmol, 58.65±18.55 µmol, and 80.43±35.44 µmol, respectively. The urine concentration of PLC was 6.63±4.50 µmol, 15.33±12.59 µmol, 15.46±6.26 µmol, 13.41±11.66 µmol and 9.67±7.92 µmol, respectively. The accumulated excretion rate of LC was 6.1% within 24h after its administration. There was also an increase in urine concentrations of SOD and T-AOC, and a decrease in NO and MDA. A positive correlation was found between urine concentrations of LC and SOD (r = 0.8277) or T-AOC (r = 0.9547), and a negative correlation was found between urine LC excretions and NO (r = -0.8575) or MDA (r = 0.7085). In conclusion, a single oral LC administration let to a gradual increase in urine L-carnitine excretion which was associated with an increase in urine antioxidant enzymes and the total antioxidant capacities. These data may be useful in designing therapeutic regimens of LC or its analogues in the future.


A excreção urinária de L-carnitina (LC), acetil-L-carnitina (ALC) e propionil-L-carnitine (PLC) e as suas relações com as atividades antioxidantes são presentemente desconhecidos. Líquido de L-carnitina (2,0 g) foi administrada por via oral como uma dose única em 12 indivíduos saudáveis. As concentrações urinárias de LC, PLC e ALC foram detectados por HPLC. Atividades superóxido dismutase (SOD), a capacidade antioxidante total (T-AOC), malondialdeído (MDA) e óxido nítrico (NO) foram medidas por métodos espectrofotométricos. O 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excreção de LC foi 53,13±31.36 µmol, 166,93±76.87 µmol, 219,92±76.30 µmol, 100,48±23.89 µmol, 72,07±25.77 µmol, respectivamente. A excreηão de ALC foi 29,70±14.43 µmol, 80,59±32.70 µmol, 109,85±49.21 µmol, 58,65±18.55 µmol, e 80,43±35.44 µmol, respectivamente. A concentraηão de urina de PLC foi 6,63±4.50 µmol, 15,33±12.59 µmol, 15,46±6.26 µmol, 13,41±11.66 µmol e 9,67±7.92 µmol, respectivamente. A taxa de excreηão acumulada de LC foi de 6,1% 24 horas após sua administração. Houve também um aumento nas concentrações de urina de SOD e T-COA e diminuição de NO e de MDA. Correlação positiva foi encontrada entre as concentrações de urina de LC e SOD (r = 0,8277) ou T-AOC (r = 0,9547) e correlação negativa entre a excreção de LC e NO (r = -0,8575) ou MDA (r = 0,7085). Em conclusão, a administração oral única de LC leva ao aumento gradual na excreção urinária de L-carnitina, que foi associada com o aumento das enzimas antioxidantes na urina e as capacidades antioxidantes totais. Estes dados podem ser úteis no futuro para o planejamento de esquemas terapêuticos de LC ou os seus análogos, no futuro.


Assuntos
Humanos , Acetilcarnitina/farmacocinética , Carnitina/farmacocinética , Antioxidantes/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos
8.
Inflamm Res ; 61(2): 127-34, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22089528

RESUMO

OBJECTIVE: The available evidence indicates that C-reactive protein (CRP) participates directly in atherosclerosis formation as an inflammatory molecule. Our previous investigation suggested that fibrinogen, fibrin and fibrinogen degradation products (FDP) produce a pro-inflammatory effect on vascular smooth muscle cells (VSMCs) through inducing CRP generation. In the present study, we observed the effect of pravastatin on CRP generation induced by fibrinogen, fibrin and FDP in rat VSMCs. METHODS: VSMCs from Sprague-Dawley rats were cultured. Fibrinogen, fibrin and FDP were used as stimulants for CRP generation. VSMCs were preincubated with pravastatin at 10, 30, 100 µM for 30 min prior to stimulation. CRP mRNA expression was studied by reverse transcription polymerase chain reaction (RT-PCR). CRP levels in the supernatant of VSMCs were measured by enzyme-linked immunosorbent assay (ELISA). CRP expression in VSMCs was examined with immunocytochemical staining. RESULTS: ELISA analysis showed that the pravastatin concentration-dependently reduced fibrinogen-, fibrin- and FDP-stimulated generation of CRP in VSMCs, with maximal inhibition of 56.6, 55.7 and 62.3%, respectively. Immunocytochemical staining and RT-PCR revealed that pravastatin inhibited protein and mRNA expression of CRP in VSMCs significantly. CONCLUSIONS: Pravastatin at the concentrations used in the present experiment has ability to relieve vascular inflammation and to restrain atherosclerotic processes via inhibiting the CRP production induced by fibrinogen, fibrin and FDP in VSMCs, which helps explain the beneficial effects of pravastatin on atherosclerosis.


Assuntos
Proteína C-Reativa/biossíntese , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Pravastatina/farmacologia , Animais , Células Cultivadas , Fibrina/farmacologia , Produtos de Degradação da Fibrina e do Fibrinogênio/farmacologia , Fibrinogênio/farmacologia , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Ratos , Ratos Sprague-Dawley
9.
Sheng Li Xue Bao ; 63(2): 164-70, 2011 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-21505732

RESUMO

The present study was conducted to investigate the effects of gossypol acetic acid (GAA) on the proliferation of human mucoepidermoid carcinoma cell line MEC-1 in vitro and its possible molecular mechanisms of DNA double-strand breaks (DSB). MTT assay was performed to test the inhibition of proliferation of MEC-1 cells by GAA. DSB and γH2AX foci formation induced by GAA were detected by neutral comet assay and immunostaining. GAA (5-40 µmol/L) inhibited the growth of MEC-1 cells in a dose- and time-dependent manner. One of the indexes of comet assay, percentage of head DNA was decreased, however other indexes, including tail length, percentage of tail DNA, tail moment (TM) and Olive tail moment (OTM) were increased when treated with 2.5- 40 µmol/L GAA for 24 h or 20 µmol/L GAA for 3-48 h, compared with those in control. The percentage of γH2AX-positive cells was also increased when MEC-1 was treated with 2.5-20 µmol/L GAA for 24 h or 20 µmol/L GAA for 3-48 h, compared with that in control. All these results show that GAA inhibits the proliferation of MEC-1, and DSB maybe one of the mechanisms of inhibitory effect of GAA on the growth of tumor cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Mucoepidermoide/patologia , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Gossipol/análogos & derivados , Carcinoma Mucoepidermoide/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Gossipol/farmacologia , Humanos , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia
10.
Atherosclerosis ; 213(1): 92-101, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20832068

RESUMO

BACKGROUND: It has been shown that angiotensin II (Ang II) is able to accelerate endothelial progenitor cells (EPCs) senescence through induction of oxidative stress. Calcitonin gene-related peptide (CGRP), a major neurotransmitter of the capsaicin-sensitive sensory nerves, protects endothelial function. Whether CGRP protects against EPCs senescence is unknown. METHODS AND RESULTS: In cord-derived EPCs, the effects of CGRP on Ang II-induced cell senescence were evaluated by exogenous application of CGRP and rutaecarpine (to stimulate the endogenous CGRP production) or by over-expression of CGRP. The anti-senescence mechanisms of CGRP on EPCs were investigated either by applying CGRP antagonist or by silence of klotho, an anti-aging protein. The results showed that both CGRP and klotho mRNA expression were reduced in Ang II-induced senescent EPCs. Exogenous application of CGRP inhibited Ang II-induced EPCs senescence by down-regulating the expression of NADPH oxidase and reactive oxygen species production. Similarly, rutaecarpine or CGRP I over-expression also inhibited Ang II-induced EPCs senescence. The effects of CGRP and rutaecarpine were reversed by CGRP(8-37), a select antagonist of CGRP receptor and capsazepine, a selective antagonist of transient receptor potential vanilloid 1, respectively. Furthermore, gene silence of klotho markedly attenuated the anti-senescence effect of CGRP on EPCs. CONCLUSIONS: The results suggest that CGRP can counteract Ang II-induced EPCs senescence through down-regulating the expression of NADPH oxidase and reactive oxygen species production and increasing the production of klotho.


Assuntos
Angiotensina II/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/fisiologia , Células Endoteliais/citologia , Regulação da Expressão Gênica , Glucuronidase/metabolismo , Células-Tronco/citologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Senescência Celular , Sangue Fetal/metabolismo , Humanos , NADPH Oxidases/metabolismo , Neurotransmissores/metabolismo , Estresse Oxidativo , Interferência de RNA , Espécies Reativas de Oxigênio , Regulação para Cima
11.
J Hypertens ; 28(5): 931-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20375903

RESUMO

OBJECTIVES: To explore whether the accelerated senescence of endothelial progenitor cells (EPCs) is related to the reduction of calcitonin gene-related peptide (CGRP) in hypertension. METHODS AND RESULTS: In-vivo studies, plasma levels of CGRP and the number of senescent EPCs were measured in hypertensive humans and animals, from which the EPCs were isolated to examine the production of CGRP. Moreover, rutaecarpine, as an agent or tool to stimulate CGRP production, was used in hypertensive animals. The effects of rutaecarpine on angiotensin II-induced EPCs senescence were evaluated in vitro. The results showed that the number of circulating senescent EPCs was significantly increased in hypertension concomitantly with the decreased plasma level of CGRP and the decreased CGRP mRNA expression in EPCs. Administration of rutaecarpine reversed EPC senescence along with an elevation in CGRP production in spontaneously hypertensive rats. In the angiotensin II-induced EPCs senescence, the CGRP mRNA expression was reduced, which was reversed by rutaecarpine. The effect of rutaecarpine on EPCs was canceled in the presence of capsazepine, a selective antagonist of transient receptor potential vanilloid 1. CONCLUSION: The results suggest that CGRP may work as an endogenous protective substance to counteract EPCs senescence in hypertension and the accelerated EPCs senescence in hypertension was related to the reduction of CGRP.


Assuntos
Células-Tronco Adultas/patologia , Peptídeo Relacionado com Gene de Calcitonina/sangue , Senescência Celular , Células Endoteliais/patologia , Hipertensão/sangue , Hipertensão/patologia , Adulto , Células-Tronco Adultas/efeitos dos fármacos , Células-Tronco Adultas/metabolismo , Angiotensina II/farmacologia , Animais , Sequência de Bases , Peptídeo Relacionado com Gene de Calcitonina/biossíntese , Peptídeo Relacionado com Gene de Calcitonina/genética , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Senescência Celular/efeitos dos fármacos , Primers do DNA/genética , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Humanos , Hipertensão/genética , Técnicas In Vitro , Alcaloides Indólicos/farmacologia , Masculino , Pessoa de Meia-Idade , Quinazolinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Canais de Cátion TRPV/genética
12.
Basic Clin Pharmacol Toxicol ; 107(2): 669-75, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20346058

RESUMO

Numerous studies have shown that C-reactive protein (CRP), a pro-inflammation cytokine, makes a direct contribution to atherosclerosis, and that (-)-epigallocatechin gallate (EGCG) is able to exert an anti-atherosclerotic effect by anti-oxidative and anti-inflammatory activities. Based on our previous study, the effect of EGCG on endothelin-1 (ET-1)-induced CRP production in rat vascular smooth muscle cells (VSMCs) and the possible mechanism were observed. The in vitro experiments showed that EGCG concentration-dependently inhibited ET-1-stimulated expression of CRP both in protein and mRNA levels in VSMCs as determined by the immunocytochemical staining, the enzyme-linked immunosorbent assay and the real-time quantitative polymerase chain reaction (RT-qPCR). The in vivo investigation with the double-labelled immunofluorescence staining and RT-qPCR displayed that EGCG also prevented ET-1-induced CRP expression in protein and mRNA levels in the aortic VSMCs of rats receiving the subchronic infusion of ET-1. In addition, EGCG suppressed reactive oxygen species (ROS) generation evoked by ET-1 in VSMCs as observed by the fluorescence probe. These demonstrate that EGCG may inhibit ET-1-stimulated generation of CRP in VSMCs so to relieve the inflammatory response and oxidative stress via blocking ROS signal, which provides new evidence for an anti-atherosclerotic effect of EGCG.


Assuntos
Antioxidantes/farmacologia , Proteína C-Reativa/metabolismo , Catequina/análogos & derivados , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aorta Torácica/citologia , Proteína C-Reativa/genética , Catequina/farmacologia , Células Cultivadas , Endotelina-1/farmacologia , Ensaio de Imunoadsorção Enzimática , Expressão Gênica/efeitos dos fármacos , Masculino , Músculo Liso Vascular/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
J Cardiovasc Pharmacol ; 55(6): 560-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20224429

RESUMO

Homocysteine plays a key role in endothelial cell senescence associated with atherosclerosis-based cardiovascular diseases. Selaginellin, a component extracted from Selaginella pulvinata (Hook. et Grev.) Maximo, was assessed for its ability to protect human umbilical vein endothelial cells against homocysteine-induced senescence. The endothelial cells were pretreated with various concentrations (10(-7), 3 x 10(-7), or 10(-6) M) of selaginellin for 1 hour before exposure to homocysteine. Selaginellin was shown to protect endothelial cells against homocysteine-induced senescence, as determined by senescence-associated beta-galactosidase activity, telomerase activity, and cell cycle distribution. In addition, the increase in levels of intracellular reactive oxygen species and downregulation of SIRT1 gene expression induced by homocysteine were significantly reversed by selaginellin. Our study suggests that selaginellin has a protective effect against homocysteine-induced senescence through mechanisms related to antioxidation via scavenging reactive oxygen species and upregulating the expression of SIRT1 gene.


Assuntos
Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ciclo Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio/metabolismo , Homocisteína/metabolismo , Homocisteína/farmacologia , Homocisteína/fisiologia , Humanos , Óxido Nítrico Sintase Tipo III , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Veias Umbilicais/metabolismo , Regulação para Cima/efeitos dos fármacos , beta-Galactosidase/metabolismo , beta-Galactosidase/farmacologia
14.
Clin Exp Pharmacol Physiol ; 37(5-6): 630-5, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20132235

RESUMO

1. It has been reported that resveratrol exerts the inhibitory effects on aging through activation of sirtuin 1 (SIRT1) and dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway involved in the high glucose-induced endothelial cell senescence. 2. The aims of this work were to explore whether BTM-0512, a novel derivative of resveratrol, was able to exert the beneficial effect on high glucose-induced cellular senescence through regulating the DDAH/ADMA pathway and to explore whether the regulatory effect of BTM-0512 on DDAH/ADMA pathway was related to the activation of SIRT1. 3. The senescence model of endothelial cells was induced by high glucose and the cells were collected for the determination of beta-galactosidase and DDAH activity, ADMA level, DDAH and SIRT1 mRNA expression. 4. The results showed that high glucose significantly increased the ratio of senescent cells concomitantly with the decreased DDAH activity, the downregulated DDAH2 and SIRT1 mRNA expressions and the increased ADMA levels, which were attenuated by pretreatment with BTM-0512. 5. The beneficial effects of BTM-0512 on high glucose-induced senescence were blocked by splimtomicin, the specific inhibitor of SIRT1, or by silencing DDAH2 expression. 6. The results suggest that BTM-0512 was able to exert the beneficial effects on high glucose-induced cellular senescence through regulating the DDAH/ADMA pathway, and its regulatory effect on DDAH/ADMA pathway was related to the activation of SIRT1.


Assuntos
Amidoidrolases/metabolismo , Antioxidantes/farmacologia , Arginina/análogos & derivados , Senescência Celular/efeitos dos fármacos , Glucose/efeitos adversos , Estilbenos/análise , Estilbenos/farmacologia , Amidoidrolases/genética , Arginina/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/enzimologia , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/metabolismo , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sirtuína 1/metabolismo
15.
Naunyn Schmiedebergs Arch Pharmacol ; 381(1): 73-81, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19936711

RESUMO

L-glutamate plays a key role in neuronal cell death associated with many neurodegenerative conditions such as cerebral ischemia, hypoxia, Alzheimer's, Huntington's, and Parkinson's diseases. Selaginellin, a component extracted from Saussurea pulvinata (Hook.et Grev.) Maximo, was assessed for its ability to protect rat pheochromocytoma (PC12) cells against oxidative toxicity induced by glutamate. The differentiated PC12 cells were pretreated with various concentrations (10(-7), 3 x 10(-7), or 10(-6) M) of selaginellin for 1 h prior to exposure to L-glutamate. Selaginellin was shown to protect PC12 cells against glutamate toxicity, as determined by characteristic morphological features, lactate dehydrogenase release and cell viability, and apoptosis as evaluated by Hoechst 33342 staining assay and caspase-3 activity. In addition, the increase in levels of reactive oxygen species and decrease in klotho gene expression induced by glutamate were significantly reversed by selaginellin. Our study suggests that selaginellin has a neuroprotective effect against L-glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis via scavenging reactive oxygen species and up-regulating the expression of klotho gene.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ácido Glutâmico/toxicidade , Extratos Vegetais/farmacologia , Saussurea , Animais , Antioxidantes/isolamento & purificação , Apoptose/fisiologia , Diferenciação Celular/fisiologia , Células PC12 , Extratos Vegetais/isolamento & purificação , Ratos , Espécies Reativas de Oxigênio/metabolismo
16.
J Asian Nat Prod Res ; 11(12): 1001-4, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20183268

RESUMO

A novel compound, selaginellin C (1), was isolated from Selaginella pulvinata Maxim (Hook et Grev.) as (R,S)-4-((1,2-dihydroxyethyl)-2',4'-dihydroxy-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)((4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone, along with two known compounds, selaginellin (2) and selaginellin A (3). The structure of the new compound was elucidated on the basis of 1D and 2D NMR as well as HR-ESI-MS spectroscopic analysis.


Assuntos
Compostos de Bifenilo/isolamento & purificação , Cicloexanonas/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Pigmentos Biológicos/isolamento & purificação , Selaginellaceae/química , Compostos de Bifenilo/química , Cicloexanonas/química , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pigmentos Biológicos/química
17.
Zhong Yao Cai ; 30(9): 1105-9, 2007 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-18236756

RESUMO

OBJECTIVE: To investigate the protective effect of Total Flavonoid of Herba Pyrolae(TFHP) on acute myocardial ischemic injury in rats. METHODS: Acute myocardial ischemic models were established by i. v. injection of pituitrin and the ligation of left descending coronary artery in rats. ECG of the rat was recorded, myocardial ischemic size was evaluated, and activites of creatine phosphokinase( CK), lactate dehydrogenase (LDH) and superoxide dismutase (SOD), level of malondialdehyde (MDA) in the rat serum were determined. RESULTS: In comparison with the model control, TFHP significantly reduced the incidence of ischemic arrhythmia induced by pituitrin, size of myocardial infarction, release of myocardial CK and LDH caused by the ligation of left descending coronary artery in rats. The primary study of action mechanism showed that TFHP decreased MDA level and increased SOD activity in the rat serum. CONCLUSION: TFHP provide a protective effect on acute myocardial ischemic injury via antioxidation.


Assuntos
Cardiotônicos/farmacologia , Flavonoides/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Pyrola/química , Animais , Arritmias Cardíacas/patologia , Arritmias Cardíacas/prevenção & controle , Cardiotônicos/uso terapêutico , Creatina Quinase/sangue , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/isolamento & purificação , Flavonoides/uso terapêutico , L-Lactato Desidrogenase/sangue , Masculino , Malondialdeído/metabolismo , Isquemia Miocárdica/sangue , Isquemia Miocárdica/induzido quimicamente , Miocárdio/metabolismo , Miocárdio/patologia , Fitoterapia , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue
18.
Pharmazie ; 60(12): 934-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16398271

RESUMO

The aim of the present study was to investigate the protective effect of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride (DDPH) on myocardial ischemia-reperfusion (I/R) injury in rats and the mechanism of its myocardial protection. For this purpose, 50 Wistar rats were divided into five groups: sham group, control group, verapamil treated group, and two DDPH treated groups (20 and 40 mg/kg, respectively). Myocardial I/R injury model was established by reperfusion for 120 min after 40 min ischemia induced by the ligation of left descending coronary artery in rats. The influence of DDPH on myocardial infarction size was observed and the levels of myocardial enzymes in serum were measured. The activities of oxygen free radical scavenging enzymes and the content of malondialdehyde (MDA) in myocardium and serum were determined. The pathological changes of myocardial tissue were observed. The results showed that DDPH significantly diminished myocardial infarction size, reduced the release of myocardial creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and glutamic oxaloacetic aminotransferase (GOT), protected the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the content of MDA in myocardium and serum as compared with the control group. The degree of myocardial injury was slighter in DDPH treated groups than in control group. These results suggest that DDPH produces a cardioprotective effect during myocardial I/R injury, which may be related to blocking calcium channels and inhibiting the formation of the oxygen free radical and subsequent peroxidation of lipid by DDPH.


Assuntos
Fármacos Cardiovasculares/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fenetilaminas/farmacologia , Animais , Aspartato Aminotransferases/sangue , Creatina Quinase/sangue , Creatina Quinase/metabolismo , Feminino , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/enzimologia , Miocárdio/patologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA