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Am J Transl Res ; 13(10): 11245-11254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786055


OBJECTIVE: To investigate the effects of lncRNA SDHAP1 on the multiplication, migration and invasiveness of NSCLC cells. METHODS: From The Cancer Genome Atlas (TCGA) database, the clinical data of NSCLC patients were retrieved to analyze the expression of lncRNA SDHAP1 in LC. In this study, lncRNA SDHAP1 in NSCLC cell lines was regulated, and its expression profiling in non- and cis-platinum (CDDP) resistant NSCLC cell lines was identified by qPCR. The levels of multidrug resistance-related protein 1 (MRP1), p-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) were measured by Western blotting (WB), the migration and invasion of LC cells were detected by Transwell assay, and the cell multiplication and activity were determined by MTT assays. RESULTS: TCGA database identified upregulated lncRNA SDHAP1 expression in LC. qPCR results revealed that lncRNA SDHAP1 was highly expressed in NSCLC. LncRNA SDHAP1 showed higher expression in patients with stage IV than in those with stage I, II or III, as well as in people aged 21-40 years old. Compared with normal lung epithelial cells, lncRNA SDHAP1 was upregulated in NSCLC cell lines, especially in those resistant to CDDP. LncRNA SDHAP1 downregulation led to a decrease in multiplication, migration and invasiveness of NSCLC cells, and a reduction in activity, migration and invasiveness of CDDP-resistant NSCLC cell lines. In addition, lncRNA SDHAP1 knockdown down-regulated the expression levels of Multidrug resistance-associated proteins MRP1, P-gp and GST-π. CONCLUSIONS: LncRNA SDHAP1 is upregulated in NSCLC and is associated with LC staging and age of patients. Silencing lncRNA SDHAP1 can suppress the multiplication, migration, invasiveness and CDDP resistance of cancer cells. Therefore, lncRNA SDHAP1 may serve as a prognostic biomarker and treatment target for NSCLC.

Cell Mol Biol Lett ; 23: 41, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30181740


Background: MicroRNAs play important roles in regulation of the cardiovascular system. The purpose of this study was to investigate microRNA-320 (miR-320) expression in myocardial ischemia-reperfusion (I/R) injury and the roles of miR-320 in cardiomyocyte apoptosis by targeting AKIP1 (A kinase interacting protein 1). Methods: The level of miR-320 was detected using quantitative real-time polymerase chain reaction (qRT-PCR), and cardiomyocyte apoptosis was detected via terminal dUTP nick end-labeling assay. Cardiomyocyte apoptosis and the mitochondrial membrane potential were evaluated via flow cytometry. Bioinformatics tools were used to identify the target gene of miR-320. The expression levels of AKIP1 mRNA and protein were detected via qRT-PCR and Western blot, respectively. Results: Both the level of miR-320 and the rate of cardiomyocyte apoptosis were substantially higher in the I/R group and H9c2 cells subjected to H/R than in the corresponding controls. Overexpression of miR-320 significantly promoted cardiomyocyte apoptosis and increased the loss of the mitochondrial membrane potential, whereas downregulation of miR-320 had an opposite effect. Luciferase reporter assay showed that miR-320 directly targets AKIP1. Moreover, knock down and overexpression of AKIP1 had similar effects on the H9c2 cells subjected to H/R. Conclusions: miR-320 plays an important role in regulating cardiomyocyte apoptosis induced by I/R injury by targeting AKIP1 and inducing the mitochondrial apoptotic pathway.

Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/genética , Miócitos Cardíacos/patologia , Animais , Apoptose , Linhagem Celular , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Ratos
Tohoku J Exp Med ; 225(1): 51-7, 2011 09.
Artigo em Inglês | MEDLINE | ID: mdl-21869591


Electrical remodeling at infarct border zone has been shown to contribute to the occurrence of ventricular arrhythmias after myocardial infarction (MI). Electrical remodeling is causally associated with sympathetic neural remodeling in MI. Semaphorin 3A (Sema3A), a potent neural chemorepellent for sympathetic axons, has been demonstrated to suppress sympathetic neural remodeling after MI. In the present study, we investigated whether treatment with Sema3A can ameliorate electrical remodeling at infarct border zones using a rat model of MI. Wistar rats underwent sham operation (n = 20), the ligation of left coronary artery (MI group, n = 30), MI with control adenovirus (Ad group, n = 30), and MI with Sema3A adenovirus (Sema3A group, n = 30). Eight weeks after treatment, electrophysiological properties including heart rate variability (HRV), monophasic action potential duration (MAPD) and effective refractory period (ERP) and the expression of arrhythmia-related ion channel proteins including Kv4.2, KChIP2 and Kir2.1 at the infarcted border of the left ventricle were examined. These channel proteins may be required for maintaining normal heart rhythm. Compared with the Ad group, Sema3A significantly increased HRV and shortened MAPD and ERP (all p < 0.05). The expression levels of Kv4.2, KChIP2 and Kir2.1 proteins were significantly decreased in MI group and Ad group, compared to sham control. In contrast, the expression levels of these proteins were restored in Sema3A group, which may represent the molecular basis of the Sema3A-mediated inhibition of electrical remodeling. In conclusion, Sema3A can ameliorate electrical remodeling at infarct border zones after MI.

Fenômenos Eletrofisiológicos , Terapia Genética , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Semaforina-3A/genética , Semaforina-3A/uso terapêutico , Remodelação Ventricular/fisiologia , Animais , Pressão Sanguínea/fisiologia , Western Blotting , Frequência Cardíaca/fisiologia , Masculino , Infarto do Miocárdio/patologia , Canais de Potássio/metabolismo , Ratos , Ratos Wistar , Coloração e Rotulagem
Zhonghua Yi Xue Za Zhi ; 88(24): 1707-10, 2008 Jun 24.
Artigo em Chinês | MEDLINE | ID: mdl-19024544


OBJECTIVE: To investigate the effects of sympathetic nerve stimulation (SNS) on connexin43 (Cx43) and ventricular arrhythmias during acute myocardial ischemia (MI). METHODS: Ninety five Wistar rats were randomly divided into four groups: MI group (n=25), undergoing: ligation of the anterior descending coronary; MII-SNS group (n=25); undergoing electric stimulation of sympathetic nerve since the beginning of ligation of the anterior descending coronary and lasting till 30 min after the ligation, sympathetic nerve stimulation preconditioning + myocardial ischemia (pSNS-MI) group (n=25), undergoing electric stimulation of sympathetic nerve since the beginning of ligation of the anterior descending coronary that ended just after the ligation; and sham operation (SO) group (n=20), without coronary ligation. Ventricular arrhythmias were monitored by electrocardiography. Western blotting and RT-PCR were used to detect the protein and mRNA expression of Cx43 respectively. Immunofluorescence analysis was used to observe the changes of Cx43 protein distribution. RESULTS: One and 3 rate died due to ventricular fibrillation in the MI group and MI-SS group respectively. The incidence of ventricular tachycardia (VT)/VF within 30-minute after ligation in the MI-SNS group was 80.0%, significant higher than that of the MI group (52.0%, P < 0.05). The incidence of VT/VF within 30-minute after ligation of the pSNS-MI group was 20.0%, significantly lower than that of the MI-SNS group (P < 0.05). 30 minutes after the ligation, the percentage of phosphorylated Cx43 of the pSNS-MI and MI-SNS groups were 71.2% +/- 7.0% and 73.4% +/- 6.7% respectively, both significantly higher than that of the MI group (46.7% +/- 6.3%) (both P < 0.05). The total contents of Cx43 of the MI and pSNS-MI groups were 1.29 +/- 0.14 and 1.25 +/- 0.13 respectively, both similar to that of the SO group [(1.30 +/- 0.10), both P > 0.05], while the total Cr43 content of the MI-SNS group was 0.73 +/- 0. 12, significantly lower than that of the SO group [(1.30 +/- 0.10), P < 0.05]. The Cx43 mRNA levels of the 3 experimental groups were all significantly lower than that of the SO group (all P < 0.05). Immunofluorescence analysis confirmed that ischemia and sympathetic nerve stimulation induced the changes of connexin43 distribution and sympathetic nerve stimulation preconditioning inhibited the changes of connexin43 distribution induced by ischemia. CONCLUSION: SNS promotes ventricular arrhythmias by promoting Cx43 degradation, and sympathetic nerve stimulation preconditioning inhibits ventricular arrhythmias by preventing Cx43 dephosphorylation.

Arritmias Cardíacas/fisiopatologia , Conexina 43/metabolismo , Isquemia Miocárdica/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Animais , Western Blotting , Conexina 43/genética , Estimulação Elétrica/métodos , Imunofluorescência , Masculino , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa
Zhonghua Xin Xue Guan Bing Za Zhi ; 34(11): 1016-20, 2006 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-17288768


OBJECTIVE: To investigate the relationship between sympathetic remodeling and electrical remodeling at the infarcted border zone (IBZ) of rabbit with chronic myocardial infarction (MI). METHODS: Thirty rabbits were randomly assigned into two groups: MI group (n = 20): ligation of the anterior descending coronary; sham operation (SO) group (n = 10): without contrary ligation. Eight weeks after surgery, transmural dispersion of repolarization (TDR) at baseline, during sympathetic nerve stimulation, TDR change (DeltaTDR) during sympathetic nerve stimulation and ventricular fibrillation threshold (VFT) were measured at the IBZ in MI group and corresponding zone in SO group. The distribution and densities of growth associated protein 43 (GAP43) and tyrosine hydroxylase (TH) positive nerves in ventricle were also detected with immunohistochemical techniques. RESULTS: Eighteen rabbits in the MI group and 10 in the SO group survived to the end of the study. The densities of GAP43 and TH at the IBZ in the MI group were significantly higher than that at the corresponding zone in the SO group (both P < 0.05). The densities of GAP43 and TH in MI rabbits positively correlated with TDR at baseline, TDR or DeltaTDR during sympathetic nerve stimulation (all P < 0.01) and both showed a weak negative correlation with VFT (r =-0.44, P = 0.07; r = -0.41, P = 0.09, respectively). CONCLUSION: Sympathetic remodeling is correlated with electrical remodeling at the IBZ in rabbits with chronic MI.

Infarto do Miocárdio/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Potenciais de Ação , Animais , Humanos , Masculino , Infarto do Miocárdio/patologia , Coelhos , Distribuição Aleatória