Zhao Y.,Capital Medical University |
Huang H.,Capital Medical University |
Du Y.,Capital Medical University |
Li X.,Capital Medical University |
And 7 more authors.
Cardiovascular Toxicology | Year: 2015
β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (IK) plays a crucial role in APD, but the effects of β1-AAs on IK have not been completely illuminated. This work aimed to observe the effects of β1-AAs on IK and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and IK were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (IKr), but similarly decreased the slowly activating delayed rectifier potassium current (IKs) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients. © 2014, Springer Science+Business Media New York. Source
Yang X.,Capital Medical University |
Zhang C.,Beijing Neurosurgical Institute |
Zhang C.,Capital Medical University |
Guo T.,Capital Medical University |
And 5 more authors.
Molecular Medicine Reports | Year: 2015
MicroRNAs are short single-stranded non-coding RNA molecules that function as regulators of tumor progression, including regulation of glioblastoma multiforme, which is a World Health Organization grade IV glioma. Based on the results of a microRNA microarray, which included 198 patients with glioma from the Chinese Glioma Genome Atlas data set, it was observed that microRNA-206 (miR-206) was downregulated in high-grade (grades III and IV) gliomas compared with grade II gliomas. In addition, high expression of miR-206 was associated with longer overall survival time in glioma patients. The present study aimed to investigate the biological functions of miR-206 in glioma progression in vitro using the LN229 glioma cell line. Cell proliferation was observed to be inhibited subsequent to transfection with miR-206. It was suggested that miR-206 induced cell cycle G1/S phase arrest by suppressing the expression of cyclinD2. The results of the present study concluded that miR-206 inhibits glioma progression via the regulation of cyclinD2 and that miR-206 may be a novel biomarker with potential for use as a therapeutic target in gliomas. Source
Ma L.,Capital Medical University |
Wang K.,Capital Medical University |
Shang J.,Capital Medical University |
Cao C.,Fujian Medical University |
And 7 more authors.
PLoS ONE | Year: 2014
Declined vasorelaxation function in aging resistance arteries is responsible for aging-related multiple organ dysfunctions. The aim of the present study is to explore the role of peroxynitrite (ONOO-) in aging resistance arterial vasorelaxation dysfunction and the possible mechanism. In the present study, young (3-4 months olds) and aging (20 months olds) male SD rats were randomized to receive vehicle (Saline) or FeTMPyP (ONOO- scavenger) for 2 weeks. The vasorelaxation of resistance arteries was determined in vitro; NOx level was tested by a colorimetric assay; the expression of nitrotyrosine (NT), soluble Guanylate Cyclase (sGC), vasodilator-stimulated phosphoprotein (VASP), phosphorylated VASP (P-VASP) and cGMP in resistance arteries were detected by immunohistochemical staining. In the present study, endothelium-dependent dilation in aging resistance arteries was lower than in those from young rats (young vs. aging: 68.0%±4.5% vs. 50.4%±2.9%, P<0.01). And the endothelium-independent dilation remained constant. Compared with young rats, aging increased nitrative stress in resistance arteries, evidenced by elevated NOx production in serum (5.3±1.0 nmol/ml vs. 3.3±1.4 nmol/ml, P<0.05) and increased NT expression (P<0.05). ONOO- was responsible for the vasorelaxation dysfunction, evidenced by normalized vasorelaxation after inhibit ONOO - or its sources (P<0.05) and suppressed NT expression after FeTMPyP treatment (P<0.05). The expression of sGC was not significantly different between young and aging resistance arteries, but the cGMP level and P-VASP/VASP ratio (biochemical marker of NO-sGC-cGKs signaling) decreased, which was reversed by FeTMPyP treatment in vivo (P<0.05). The present study suggested that ONOO- mediated the decline of endothelium-dependent vasorelaxation of aging resistance arteries by induction of the NO-sGC-cGKs pathway dysfunction. © 2014 Ma et al. Source
Liu D.,Capital Medical University |
Liu X.,Capital Medical University |
Wu Y.,Capital Medical University |
Wang W.,Capital Medical University |
And 4 more authors.
International Journal of Molecular Sciences | Year: 2016
HtrA serine peptidase 2 (HtrA2), also named Omi, is a pro-apoptotic protein that exhibits dramatic changes in expression levels in a variety of disorders, including ischemia/reperfusion injury, cancer, and neurodegeneration. In our study, Omi/HtrA2 protein levels were high in the heart, brain, kidney and liver, with elevated heart/brain expression in aging mice. A similar expression pattern was observed at the mRNA level, which suggests that the regulation of Omi/HtrA2 is predominately transcriptional. Promoter binding by transcription factors is the main influencing factor of transcription, and to identify specific promoter elements that contribute to the differential expression of mouse Omi/HtrA2, we constructed truncated Omi/HtrA2 promoter/luciferase reporter vectors and analyzed their relative luciferase activity; it was greatest in the promoter regions at -1205~-838 bp and -146~+93 bp, with the -838~-649 bp region exhibiting negative regulatory activity. Bioinformatics analysis suggested that the Omi/HtrA2 gene promoter contains a CpG island at-709~+37 bp, and eight heat shock transcription factor 1 (HSF1) sites, two Sp1 transcription factor (SP1)sites, one activator protein (AP) site, seven p53 sites, and four YY1 transcription factor(YY1) sites were predicted in the core areas. Furthermore, we found that p53 and HSF1 specifically binds to the Omi/HtrA2 promoter using chromatin immunoprecipitation analysis. These results provide a foundation for understanding Omi/HtrA2 regulatory mechanisms, which could further understanding of HtrA-associated diseases. © 2016 by the authors; licensee MDPI, Basel, Switzerland. Source