RESUMO
The programmed cell death 4 (Pdcd4), a translation inhibitor, plays an essential role in tumor suppression, but its role in apoptosis remains unclear. Here we show that Pdcd4 is a critical suppressor of apoptosis by inhibiting the translation of procaspase-3 mRNA. Pdcd4 protein decreased more rapidly through microRNA-mediated translational repression following apoptotic stimuli than did the activation of procaspase-3, cleavage of poly(ADP)ribose polymerase (PARP) by active caspase-3, and nuclear fragmentation. Strikingly, the loss of Pdcd4 by the specific RNA interference increased procaspase-3 expression, leading to its activation and PARP cleavage even without apoptotic stimuli, and sensitized the cells to apoptosis. Thus, our findings provide insight into a novel mechanism for Pdcd4 as a regulator of apoptosis.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/fisiologia , Caspase 3/biossíntese , Regulação Enzimológica da Expressão Gênica/fisiologia , Biossíntese de Proteínas/fisiologia , Proteínas de Ligação a RNA/metabolismo , Proteínas Reguladoras de Apoptose/genética , Caspase 3/genética , Células HeLa , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
A new facile method for monoacylation of diols has been developed. A variety of cyclic and acyclic diols, in particular 1,2-diols, were selectively monobenzoylated in good yields by the reaction with benzoyl chloride in the presence of a catalytic amount of dimethyltin dichloride and inorganic bases such as potassium carbonate. Furthermore, the method was successfully applied to a kinetic resolution of racemic 1-phenyl-1,2-ethanediol using a chiral organotin catalyst. The ee was dependent on the kind of base, water as an additive, and the reaction temperature.
Assuntos
Hospitalização , Relações Médico-Paciente , Administração de Caso , Humanos , Medicina , EspecializaçãoRESUMO
The effects of the prostacyclin analog beraprost sodium on motor nerve function and nerve blood-flow were examined in streptozotocin-induced diabetic rats. Oral administration of beraprost sodium 0.1 mg/kg/day for 8 wks significantly (P < 0.001) improved caudal motor nerve conduction velocity and sciatic nerve blood-flow, both of which are impaired in diabetic rats. Beraprost sodium did not affect glucose, sorbitol, or fructose levels in the sciatic nerve. However, a decreased content of cyclic AMP in the sciatic nerve and higher level of thromboxane B2 in the thoracic aorta of diabetic rats, as compared with those in normal rats, were reversed by the treatment with beraprost sodium (P < 0.01). Results suggest that beraprost sodium may have value in treating diabetic neuropathy, mainly by improving endoneurial blood-flow.