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Aim To explore the important role of HDAC5 in P-gp expression in rats in high-altitude low oxygen environment and its effect on phenytoin sodium pharmacokinetics. Methods Wistar rats were transported to Batang, Yushu, Qinghai, at an altitude of 4010 m, with 6 rats in each group, divided into 1 d and 3 d groups. Different groups were given phenytoin, phenytoin combined with hypericin, and phenytoin combined with verapamil. Plasma and liver tissues were collected at different time after taking the drug in the plateau area. The concentration of phenytoin sodium in plasma was determined by UFLC-MS method. Changes in protein expression were detected by Western blot. Results The results of UFLC-MS showed that the AUC
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AIM:To investigate the angiogenic effect and mechanisms of astragaloside IV(AS-IV)in rats with myocardial infarction via protein kinase D 1(PKD1)-histone deacetylase 5(HDAC5)-vascular endothelial growth factor (VEGF)signaling pathway.METHODS:The classic model of myocardial infarction by ligation of the left anterior de-scending coronary artery was replicated,and the rats were randomly divided into model group,AS-IV group,and AS-IV+CID755673(PKD1 inhibitor)group.The sham operation control group and DMSO control group were also set up.All the rats were given intravenous injection via caudal vein.The rats were sacrificed 4 weeks later,and segmental heart samples were used for HE staining and Masson staining.The expression of PKD1,HDAC5 and VEGF was analyzed by immunohis-tochemistry,RT-PCR and and Western blot.RESULTS:Compared with sham operation group and DMSO group,the myo-cardium in model group showed disordered arrangement, accompanied with necrotic myocardial cells and obvious fibrosis tissue.After treatment with AS-IV,the morphological changes of myocardium were obviously improved,and the number of new blood vessels increased significantly.However,after treatment with AS-IV+CID755673,the myocardial tissues of the rats became disordered again,with increased necrotic cells and some closed vessels.The mRNA and protein expression of PKD1,HDAC5 and VEGF in myocardial tissue in model group was significantly lower than that in sham operation and DMSO groups(P<0.05).The expression in AS-IV group was significantly higher than that in model group(P<0.01), while that in AS-IV+CID755673 group was significantly lower than that in AS-IV group(P<0.05).CONCLUSION:AS-IV promotes the angiogenesis of myocardial tissues in the rats after myocardial infarction partly by regulating the PKD 1-HDAC5-VEGF signaling pathway.
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OBJECTIVE@#To explore the impact of electroacupuncture (EA) on the AMPKα-HDAC5-HIF-1α signaling in the heart of the rats with myocardial ischemia (MI) via detecting the expressions of AMP-activated protein kinase α (AMPKα), histone deacetylase 5 (HDAC5), hypoxia inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF).@*METHODS@#Thirty-six healthy male SD rats were randomized into a sham operation group (6 rats), a sham + EA group (6 rats), a model group (12 rats) and an EA group (12 rats). We ligated the left anterior descending artery (LAD) for MI model, and exposed the heart of rats after opening the chest without ligation for the rats in the sham operation gorup and the sham + EA group. On the 2nd day after LAD ligation, EA was applied at "Neiguan" (PC 6) with 2 Hz/15 Hz and 1.5-2 mA for 30 min in the EA group and sham+EA group, once a day for 4 days. The same fixation was used in the sham operation group and the model group, without EA. Myocardial infarction area was observed by TTC staining and serum cardiac troponin T (cTnT) was detected by radioimmunoassay. The expression of VEGF mRNA was detected by real time PCR. The protein expressions of AMPKα, HDAC5, HIF-1α and VEGF were detected by western blot.@*RESULTS@#Compared with the sham operation group, 4 days after LAD ligation, the myocardial infarction was obvious and the expression of serum cTnT increased in the model group (0.05). After EA for 4 days, the myocardial infarction area and cTnT expression decreased in the EA group (both <0.01); the VEGF mRNA and protein expressions and AMPKα, HDAC5, HIF-1α protein expressions increased (<0.05, <0.01).@*CONCLUSION@#EA could regulate the AMPKα-HDAC5-HIF-1α signaling in myocardial tissue, which may activate VEGF expression for angiogenesis signaling, reduce myocardial infarction area so as to achieve cardioprotective effect.
Subject(s)
Animals , Male , Rats , AMP-Activated Protein Kinases , Electroacupuncture , Histone Deacetylases , Hypoxia-Inducible Factor 1, alpha Subunit , Myocardial Ischemia , Rats, Sprague-Dawley , Signal Transduction , Vascular Endothelial Growth Factor AABSTRACT
Objective: To investigate HDAC5 expression in gastric cancer cell lines and its effects on the proliferation and apoptosis of the gastric cancer line SGC-7901. Methods: The expression patterns of HDAC5 and Twist1 in gastric cancer cell lines and normal gastric mucosal cells were detected by Western blot. The effects of HDAC5 and Twist1 on the proliferation and apoptosis of SGC-7901 cells were analyzed by MTT and flow cytometry, respectively. Results: The expression of HDAC5 and Twist1 in gastric cancer cell lines were significantly higher than that in normal gastric mucosal cells (P<0.05). HDAC5 knockdown significantly down-regulated Twist1 expression,inhibited cell proliferation, and induced apoptosis in SGC-7901 cells, whereas HDAC5 overexpression exhibited an opposite effect (P<0.05). Moreover, Twist1 knockdown significantly inhibited cell proliferation and induced apoptosis in SGC-7901 cells (P<0.05). Conclusion:HDAC5 may promote cell proliferation and inhibit apoptosis in gastric cancer cells by upregulating Twist1 expression, thus promoting the initiation and development of gastric cancer.