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Dr. Samuel Cota Teixeira Dr. Daiana Silva Lopes Marcelo Santos da Silva Felipe Andrés Cordero da Luz Dr. Sarah Natalie Cirilo Gimenes Bruna Cristina Borges Aline Alves da Silva Flávia Alves Martins Dr. Marlus Alves dos Santos Dr. Thaise Lara Teixeira Dr. Ricardo A. Oliveira Dr. Veridiana de Melo Rodrigues Ávila Dr. Marcelo José Barbosa Silva Dr. Maria Carolina Elias Dr. René Martin Prof. Dr. Claudio Vieira da Silva Prof. Dr. Hans-Joachim Knölker 《Chembiochem : a European journal of chemical biology》2019,20(18):2390-2401
Class 1 myosins (Myo1s) were the first unconventional myosins identified and humans have eight known Myo1 isoforms. The Myo1 family is involved in the regulation of gene expression, cytoskeletal rearrangements, delivery of proteins to the cell surface, cell migration and spreading. Thus, the important role of Myo1s in different biological processes is evident. In this study, we have investigated the effects of pentachloropseudilin (PClP), a reversible and allosteric potent inhibitor of Myo1s, on angiogenesis. We demonstrated that treatment of cells with PClP promoted a decrease in the number of vessels. The observed inhibition of angiogenesis is likely to be related to the inhibition of cell proliferation, migration and adhesion, as well as to alteration of the actin cytoskeleton pattern, as shown on a PClP-treated HUVEC cell line. Moreover, we also demonstrated that PClP treatment partially prevented the delivery of integrins to the plasma membrane. Finally, we showed that PClP caused DNA strand breaks, which are probably repaired during the cell cycle arrest in the G1 phase. Taken together, our results suggest that Myo1s participate directly in the angiogenesis process. 相似文献
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目的: 探讨内质网相关降解蛋白Derlin-1对人结肠癌SW480细胞凋亡的影响及其可能的作用机制。方法: 采用sh-Derlin-1-pGPU6/Neo质粒转染构建瞬时敲除Derlin-1基因的SW480细胞株,应用实时定量PCR和免疫印迹验证Derlin-1基因和蛋白的低表达,采用CCK8法检测SW480细胞增殖情况,流式细胞仪检测SW480细胞凋亡情况,Western blot检测SW480细胞中凋亡蛋白Bcl-2、Bax表达量和ERK磷酸化水平。结果: 使用pGPU6/Neo载体能够稳定地抑制SW480细胞中Derlin-1的表达,sh-Derlin-1组细胞增殖率相对于对照组显著降低、凋亡率显著升高(P<0.05),Western blot实验结果发现sh-Derlin-1组细胞中Bcl-2表达量显著降低、Bax表达量显著升高及ERK磷酸化水平显著降低,与对照组相比差异有统计学意义(P<0.05)。结论: Derlin-1表达的降低能抑制ERK信号通路活化,进而诱导人结肠癌SW480细胞凋亡、抑制增殖。 相似文献
995.
Bradley Miller Tatiana Y. Kostrominova Aron M. Geurts Andrey Sorokin 《International journal of molecular sciences》2021,22(10)
The ubiquitously expressed adaptor protein Shc exists in three isoforms p46Shc, p52Shc, and p66Shc, which execute distinctly different actions in cells. The role of p46Shc is insufficiently studied, and the purpose of this study was to further investigate its functional significance. We developed unique rat mutants lacking p52Shc and p46Shc isoforms (p52Shc/46Shc-KO) and carried out histological analysis of skeletal and cardiac muscle of parental and genetically modified rats with impaired gait. p52Shc/46Shc-KO rats demonstrate severe functional abnormalities associated with impaired gait. Our analysis of p52Shc/46Shc-KO rat axons and myelin sheets in cross-sections of the sciatic nerve revealed the presence of significant anomalies. Based on the lack of skeletal muscle fiber atrophy and the presence of sciatic nerve abnormalities, we suggest that the impaired gait in p52Shc/46Shc-KO rats might be due to the sensory feedback from active muscle to the brain locomotor centers. The lack of dystrophin in some heart muscle fibers reflects damage due to dilated cardiomyopathy. Since rats with only p52Shc knockout do not display the phenotype of p52Shc/p46Shc-KO, abnormal locomotion is likely to be caused by p46Shc deletion. Our data suggest a previously unknown role of 46Shc actions and signaling in regulation of gait. 相似文献
996.
Skin color is determined by the processes of melanin synthesis and distribution. Problems in various molecules or signaling pathways involved in melanin synthesis contribute to skin pigmentation defects. Several trials have been conducted on the production of pigmentation-regulating agents, and drug repositioning has emerged as a modern technique to identify new uses for existing drugs. Our research team has researched substances or drugs associated with pigmentation control and, as a result, nilotinib, sorafenib, and ICG-001 have been found to promote pigmentation, while 5-iodotubercidin inhibits pigmentation. Therefore, these substances or medications were suggested as potential therapeutics for pigmentation disorders by drug repositioning. 相似文献
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Barbora Boansk Monika Bartekov Kristína Ferenczyov Mria Fogarassyov Lucia Kindernay Miroslav Baran
ík 《International journal of molecular sciences》2021,22(9)
Several mechanisms may contribute to cardiovascular pathology associated with diabetes, including dysregulation of matrix metalloproteinases (MMPs). Quercetin (QCT) is a substance with preventive effects in treatment of cardiovascular diseases and diabetes. The aim of the present study was to explore effects of chronic QCT administration on changes in heart function in aged lean and obese Zucker Diabetic Fatty (ZDF) rats and that in association with MMPs. Signaling underlying effects of diabetes and QCT were also investigated. In the study, we used one-year-old lean and obese ZDF rats treated for 6 weeks with QCT. Results showed that obesity worsened heart function and this was associated with MMP-2 upregulation, MMP-28 downregulation, and inhibition of superoxide dismutases (SODs). Treatment with QCT did not modulate diabetes-induced changes in heart function and MMPs. However, QCT activated Akt kinase and reversed effects of diabetes on SODs inhibition. In conclusion, worsened heart function due to obesity involved changes in MMP-2 and MMP-28 and attenuation of antioxidant defense by SOD. QCT did not have positive effects on improvement of heart function or modulation of MMPs. Nevertheless, its application mediated activation of adaptive responses against oxidative stress through Akt kinase and prevention of diabetes-induced negative effects on antioxidant defense by SODs. 相似文献
1000.
利用6-羟基多巴胺(6-Hydroxydopamine,6-OHDA)诱导分化型PC12细胞构建的帕金森病(Parkinson’s Disease,PD)体外细胞模型,研究了从积雪草中提取的微量皂苷(Centella Asiatica Saponins-1,CA-1)的神经保护作用。通过高分辨二级质谱鉴定化学结构、分析了积雪草中常用皂苷和CA-1对PC12细胞存活率的影响,进一步通过半定量和实时定量聚合酶链式反应、蛋白印迹等技术检测PC12细胞中相关基因和蛋白表达。结果表明在该模型中100 μmol/L CA-1、积雪草苷(Asiaticoside,AS)、羟基积雪草苷(Madecassoside,MA)分别将细胞存活率提高了28.63%、16.69%、17.54%,CA-1的神经保护作用强于AS和MA(p<0.05)。与模型组相比,CA-1剂量依赖性地提高了6-OHDA诱导PC12细胞的存活率且在CA-1浓度为25 μmol/L与模型组有显著差异(p<0.05),降低了细胞内活性氧(Reactive Oxygen Species,ROS)的水平,上调了Sod1、Cat、Bcl2基因表达。蛋白印迹法(Western Blot,WB)显示,CA-1提高了p85、PDK1、Akt的蛋白表达水平。在该研究中明确了CA-1的神经保护作用揭示了其作用可能通过PI3K/Akt信号通路。 相似文献