Endothelial nitric oxide synthase (-786T>C) and endothelin-1 (5665G>T) gene polymorphisms as vascular dysfunction risk factors in sickle cell anemia

We thank the patients for their participation because without them, this study would not have been conducted.Submitted by Éder Freyre ([email protected]) on 2017-02-13T11:47:48Z No. of bitstreams: 1 ve_Wendell_Vilas-Boas_etal_CPqGM_2016 .pdf: 691946 bytes, checksum: 0913753e32f3eeb2404666e32d916a29 (MD5)Approved for entry into archive by Éder Freyre ([email protected]) on 2017-02-13T12:20:03Z (GMT) No. of bitstreams: 1 ve_Wendell_Vilas-Boas_etal_CPqGM_2016 .pdf: 691946 bytes, checksum: 0913753e32f3eeb2404666e32d916a29 (MD5)Made available in DSpace on 2017-02-13T12:20:03Z (GMT). No. of bitstreams: 1 ve_Wendell_Vilas-Boas_etal_CPqGM_2016 .pdf: 691946 bytes, checksum: 0913753e32f3eeb2404666e32d916a29 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação de Hematologia e Hemoterapia da Bahia, Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade do Estado da Bahia, Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Analises Clínicas e Toxicologicas. Salvador, BA, Brasil.Sickle cell anemia (SCA) patients have vascular complications, and polymorphisms in endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) genes were associated with ET-1 and nitric oxide disturbance. We investigate the association of ET-1 5665G>T and eNOS -786T>C polymorphisms with soluble adhesion molecules (sVCAM-1 and sICAM-1), biochemical markers, and medical history. We studied 101 SCA patients; carriers of eNOS minor allele (C) had the highest levels of sVCAM-1, and carriers of ET-1 minor allele had more occurrence of acute chest syndrome (ACS). The multivariate analysis suggested the influence of the ET-1 gene on ACS outcome and an association of the eNOS gene with upper respiratory tract infection. We suggest that eNOS and ET-1 gene polymorphisms can influence SCA pathophysiology and that eNOS variant in SCA patients might be important to nitric oxide activity and vascular alteration. We found an association of the ET-1 minor allele in ACS, showing the importance of genetic screening in SCA

Flavonoids suppress human glioblastoma cell growth by inhibiting cell metabolism, migration, and by regulating extracellular matrix proteins and metalloproteinases expression

International audienceThe malignant gliomas are very common primary brain tumors with poor prognosis, which require more effective therapies than the current used, such as with chemotherapy drugs. In this work, we investigated the effects of several polyhydroxylated flavonoids namely, rutin, quercetin (F7), apigenin (F32), chrysin (F11), kaempferol (F12), and 3',4'-dihydroxyflavone (F2) in human GL-15 glioblastoma cells. We observed that all flavonoids decreased the number of viable cells and the mitochondrial metabolism. Furthermore, they damaged mitochondria and rough endoplasmic reticulum, inducing apoptosis. Flavonoids also induced a delay in cell migration, related to a reduction in filopodia-like structures on the cell surface, reduction on metalloproteinase (MMP-2) expression and activity, as well as an increase in intra- and extracellular expression of fibronectin, and intracellular expression of laminin. Morphological changes were also evident in adherent cells characterized by the presence of a condensed cell body with thin and long cellular processes, expressing glial fibrillary acidic protein (GFAP). Therefore, these flavonoids should be tested as potential antitumor agents in vitro and in vivo in other malignant glioma models