Assuntos
Inibidores da Angiogênese/farmacologia , Células Ependimogliais/efeitos dos fármacos , Expressão Gênica/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Actinas/genética , Proteínas Angiogênicas/genética , Apoptose , Proteínas Reguladoras de Apoptose/genética , Bevacizumab/farmacologia , Proteínas de Transporte/genética , Linhagem Celular , Sobrevivência Celular , Células Ependimogliais/metabolismo , Proteína Glial Fibrilar Ácida/genética , Humanos , Inflamação/genética , Potencial da Membrana Mitocondrial/fisiologia , Estresse Oxidativo/genética , Ranibizumab/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão/farmacologiaRESUMO
Mitochondrial (mt) DNA can be classified into haplogroups, which represent populations with different geographic origins. Individuals of maternal African backgrounds (L haplogroup) are more prone to develop specific diseases compared those with maternal European-H haplogroups. Using a cybrid model, effects of amyloid-ß (Amyß), sub-lethal ultraviolet (UV) radiation, and 5-Aza-2'-deoxycytidine (5-aza-dC), a methylation inhibitor, were investigated. Amyß treatment decreased cell metabolism and increased levels of reactive oxygen species in European-H and African-L cybrids, but lower mitochondrial membrane potential (ΔΨM) was found only in African-L cybrids. Sub-lethal UV radiation induced higher expression levels of CFH, EFEMP1, BBC3, and BCL2L13 in European-H cybrids compared to African-L cybrids. With respect to epigenetic status, the African-L cybrids had (a) 4.7-fold higher total global methylation levels (p = 0.005); (b) lower expression patterns for DNMT3B; and (c) elevated levels for HIST1H3F. The European-H and African-L cybrids showed different transcription levels for CFH, EFEMP1, CXCL1, CXCL8, USP25, and VEGF after treatment with 5-aza-dC. In conclusion, compared to European-H haplogroup cybrids, the African-L cybrids have different (i) responses to exogenous stressors (Amyß and UV radiation), (ii) epigenetic status, and (iii) modulation profiles of methylation-mediated downstream complement, inflammation, and angiogenesis genes, commonly associated with various human diseases.