RESUMO
The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3-q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway.
Assuntos
Flavoproteínas/genética , Regulação da Expressão Gênica/fisiologia , Proteínas de Membrana/genética , Proteínas Mitocondriais , Proteínas/genética , Proteína Supressora de Tumor p53/fisiologia , Difosfato de Adenosina/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Fator de Indução de Apoptose , Proteínas Reguladoras de Apoptose , Sequência de Bases , Sítios de Ligação , Mapeamento Cromossômico , Cromossomos Humanos Par 10 , Clonagem Molecular , DNA , Genes Reporter , Humanos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Proteínas/química , RNA Mensageiro/genética , Homologia de Sequência de Aminoácidos , Células Tumorais CultivadasRESUMO
Vascular and neural systems are highly interdependent, as evidenced by the wealth of intrinsic modulators shared by the two systems. We tested the hypothesis that pinacidil, a selective agonist for the SUR2B receptor found on smooth muscles, could serve as an independent means of inducing vasodilation and increased local blood volume to emulate functional hyperemia. Application of pinacidil induced vasodilation and increased blood volume in the in vivo neocortex in anesthetized rats and awake mice. Direct application of this agent to the in vitro neocortical slice had no direct impact on biophysical properties of neurons or astrocytes assessed with whole-cell recording. These findings suggest that pinacidil provides an effective and selective means for inducing hyperemia in vivo, and may provide a useful tool in directly testing the impact of hemodynamics on neural activity, as recently predicted by the hemo-neural hypothesis.