Navegando por Autor "Vessoni, Alexandre Teixeira"
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Item Chloroquine - induced glioma cells death is associated with mitochondrial membrane potential loss, but not oxidative stress.(2015) Vessoni, Alexandre Teixeira; Quinet, Annabel; Lima, Leonardo Carmo de Andrade; Martins, Davi Jardim; Garcia, Camila Carrião Machado; Rocha, Clarissa Ribeiro Reily; Vieira, Debora Braga; Menck, Carlos Frederico MartinsChloroquine (CQ), a quinolone derivative widely used to treat and prevent malaria, has been shown to exert a potent adjuvant effect when combined with conventional glioblastoma therapy. Despite inducing lysosome destabilization and activating p53 in human glioma cells, the mechanisms under lying cell death induced by this drug are poorly under stood. Here, we analyzed inatime – anddose – dependent manner, the effects of CQ up on mitochondria integrity, autophagy regulation and redox processes in four human glioma cell lines that differin their resistance to this drug. NAC – containing media protected cells against CQ-induced loss of mitochondrial membrane potential (MMP), autophagyic vacuoles (LC3II) accumulation and loss of cell viability induced by CQ. However, we noticed that part of this protection was due to media acidification in NAC preparations, alerting for problems in experimental procedures using NAC. The results indicate that although CQ induces accumulation of LC3II, mitochondria, and oxidative stress, neither of these events is clearly correlated to cell death induced by this drug. The only event elicited in all cell lines at equitoxic doses of CQ was the loss of MMP, indicating that mitochondrial stability is important for cells resistance to this drug. Finally, the data indicate that higher steady-state MMP values can predict cell resistance to CQ treatment.Item Cockayne Syndrome : the many challenges and approaches to understand a multifaceted disease.(2020) Vessoni, Alexandre Teixeira; Guerra, Camila Chaves Coelho; Kajitani, Gustavo Satoru; Nascimento, Lívia Luz de Souza; Garcia, Camila Carrião MachadoThe striking and complex phenotype of Cockayne syndrome (CS) patients combines progeria-like features with developmental deficits. Since the establishment of the in vitro culture of skin fibroblasts derived from patients with CS in the 1970s, significant progress has been made in the understanding of the genetic alterations associated with the disease and their impact on molecular, cellular, and organismal functions. In this review, we provide a historic perspective on the research into CS by revisiting seminal papers in this field. We highlighted the great contributions of several researchers in the last decades, ranging from the cloning and characterization of CS genes to the molecular dissection of their roles in DNA repair, transcription, redox processes and metabolism control. We also provide a detailed description of all pathological mutations in genes ERCC6 and ERCC8 reported to date and their impact on CS-related proteins. Finally, we review the contributions (and limitations) of many genetic animal models to the study of CS and how cutting-edge technologies, such as cell reprogramming and state-of-the-art genome editing, are helping us to address unanswered questions.