RESUMO
XPC deficiency is associated with mitochondrial dysfunction, increased mitochondrial H2O2 production and sensitivity to the Complex III inhibitor antimycin A (AA), through a yet unclear mechanism. We found an imbalanced expression of several proteins that participate in important mitochondrial function and increased expression and phosphorylation of the tumor suppressor p53 in Xeroderma pigmentosum complementation group C (XP-C) (XPC-null) cells compared with an isogenic line corrected in locus with wild-type XPC (XPC-wt). Interestingly, inhibition of p53 nuclear import reversed the overexpression of mitochondrial proteins, whereas AA treatment increased p53 expression more strongly in the XP-C cells. However, inhibition of p53 substantially increased XP-C cellular sensitivity to AA treatment, suggesting that p53 is a critical factor mediating the cellular response to mitochondrial stress. On the other hand, treatment with the antioxidant N-acetylcysteine increased glutathione concentration and decreased basal H2O2 production, p53 levels and sensitivity to AA treatment in the XPC-null back to the levels found in XPC-wt cells. Thus, the results suggest a critical role for mitochondrially generated H2O2 in the regulation of p53 expression, which in turn modulates XP-C sensitivity to agents that cause mitochondrial stress.
Assuntos
Proteínas de Ligação a DNA/genética , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Transformada , HumanosRESUMO
Foram estudados os liquidos cefalorraquidianos de 48 casos de sarampo sem evidencia clinica de envolvimento do sistema nervoso central (SNC). Encontrou-se hiperglicorraquia em 75,75% dos casos quando comparados a glicemia. Houve alteracao na frequencia da hiperglicorraquia relativa ao grau de nutricao. Nao houve relacao com a idade, tipo de complicacao, gravidade, tempo de evolucao da doenca e uso de hidratacao venosa. Estudou-se tambem a medicacao corrente que poderia modificar as cifras de glicose, assim como se valorizou a hipoglicemia de desnutricao.Foram feitas necropsias de dois casos sem alteracoes neurologicas clinicas que revelaram alteracoes a microscopia do SNC. Concluiu-se que no sarampo pode existir aumento da glicorraquia em relacao a glicemia sugerindo comprometimento subclinico do SNC