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Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells. Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins. Thus, targeting myosin-actin molecular motor is considered as a promising strategy for anti-cancer. In this study, we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics
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Objective To investigate the effect of urotensin Ⅱ on myocardial fibrosis in rats.Methods The pressure overload animal model was established in rats by abdominal aorta coarctation.The rats were divided into sham operation group,modeled for 4,8 and 12 weeks group.The expression of U Ⅱ,GPR14,col-Ⅰ,col-Ⅲ,and PKA in cardiac tissues was detected by Western blot.Isolated and cultured cardiac myofibroblasts (CFs) from new-born SD rats were treated with U Ⅱ,KT5720 or SB-611812,and then the proliferation of CFs was observed by micro scope and CKK-8.Results The expression of U Ⅱ,GPR14,col-Ⅰ,col-Ⅲand PKA increased markedly in cardiac tissues of model rat,which were time-dependent.U Ⅱ promoted the proliferation of CFs (P＜0.05),which could be inhibited by KT5720 or SB-611812.Conclusions U Ⅱ/UT system promotes the occurring and development of myocardial fibrosis.
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AIM To study the effects of Phe-Met-Arg-Phe-NH2 (FMRFa) on Na+/Ca2+ exchange and its specificity for Na+/Ca2+ exchange in rat ventricular myocytes. METHODS Na+/Ca2+ exchange current and other currents of ion channels were measured using whole cell voltage clamp techniques. RESULTS A dose-related inhibition of tetrapeptide FMRFa on Na+/Ca2+ exchange was observed in rat ventricular myocytes. Inward and outward INa+/Ca2+ were inhibited by 60.1% and 56.5%, respectively, at highest concentration (100 μmol*L-1) and its IC50 were 20 μmol*L-1 and 34 μmol*L-1 in inward and outward INa+/Ca2+, respectively. Inward and outward INa+/Ca2+ were inhibited 38.7% and 34.9%, respectively, at FMRFa 5 μmol*L-1. FMRFa 5 μmol*L-1 and 20 μmol*L-1 did not affect L-type calcium current, sodium current, transient outward current and inward rectifier potassium current. CONCLUSION These data indicate that FMRFa is a specific inhibitor of Na+/Ca2+ exchange in intact rat ventricular myocytes.
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Aim To study the receptor mechanism of carvedilol(CAR) on heart failure.Methods Established rat model of heart failure was induced by abdominal aortic coarctation.With modified Langendorff model of rat,isoproterenol(ISO),carvedilol,propranolol(PRL) and the specific ?3 adrenergic receptor(?3AR) blocker SR59230A were given perfusion on heart failure and normal rats' hearts.Then the cardiac function was investigated.At the same time,plasma norepinephrine in normal and heart failure group was measured.Results ① The ?dp/dtmax of heart failure group were significantly reduced compared with those of the normal group,and the norepinephrine level was remarkably higher than that of the normal group.② In heart failure group,perfused PRL on the basis of ISO,the maximum rate of left ventricular pressure rise(+dp/dtmax) decreased by 40.37%? 2.52%,the maximum rate of left ventricular pressure decrease(-dp/dtmax) reduced by 41.36%?1.10%;perfused CAR on the basis of ISO,+dp/dtmax decreased by 24.73%? 3.60%,-dp/dtmax reduced by 22.05%?1.27%.There were differences between these two groups,and the cardiac function perfused CAR was better than PRL.③ Perfused CAR in heart failure group,+dp/dtmax increased by 41.57%?14.98%,-dp/dtmax increased by 33.39%?6.41%;perfused ?3AR specific blocker SR59230A,+dp/dtmax increase by 45.75% ?2.64%,-dp/dtmax increased by 42.81% ?9.62%.There were no differences between these two groups.Conclusion Another receptor mechanism of CAR in heart failure model was probably blocked by ?3AR.