RESUMEN
BACKGROUND: Chronic alcohol consumption may act as a cellular stressor for brain cells, as has been found for aging. In this study we examined one component of the cellular stress response (heat shock proteins) as a function of age and alcohol exposure. We have found that the level of constitutively expressed heat shock protein 70 (heat shock cognate 70, or Hsc70) increases in the aged rat brain. Among many heat shock proteins and molecular chaperones, Hsc70 might be important not only for the normal protein folding pathway but also for refolding of denatured proteins produced by mild and chronic stress. METHODS: Male Wistar rats that were 5.5 to 28.5 months old were fed a liquid diet that contained 5% (w/v) alcohol or a control diet for 6 weeks. The effects of alcohol consumption and aging on the expression of Hsc70 in the brain were investigated. The cytosol proteins in the 12,000 x g supernatant fraction were heat-treated at 42 degrees C for 1 hr. After the heat treatment, proteins that transferred from the soluble to insoluble aggregated fraction were estimated as heat-unstable proteins. RESULTS: In the 24- and 30-month-old rat brain, chronic consumption of alcohol increased levels of Hsc70 and heat-unstable proteins. On the other hand, those changes were not detected in the younger rat brain. CONCLUSION: Chronic alcohol intake causes a stress response in the aged rat brain. It is thought that the increased level of Hsc70 is brought about by an increase of denatured proteins.
Asunto(s)
Envejecimiento/metabolismo , Consumo de Bebidas Alcohólicas/metabolismo , Encéfalo/metabolismo , Estrés Fisiológico/inducido químicamente , Estrés Fisiológico/metabolismo , Factores de Edad , Envejecimiento/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Proteínas del Choque Térmico HSC70 , Proteínas HSP70 de Choque Térmico/biosíntesis , Masculino , Ratas , Ratas WistarRESUMEN
Novel peptides homing to angiogenic vessels were recently isolated from a phage-displayed random pentade-capeptide library, and peptides having WRP sequence showed tumor growth suppression. In this study, we observed that another novel sequence, PVVLFPLH, suppressed tumor growth in vivo. Through the study of tumor growth suppression by the 5-mer peptides derived from this sequence, we determined the epitope sequence to be LFPLH. LFPLH, but not the shuffled peptide FHLLP, suppressed the migration of vascular endothelial growth factor-stimulated human umbilical vein endothelial cells. Interestingly, growth suppression of LFPLH against the cells as well as tumor cells was not observed in vitro. Therefore LFPLH may function to induce tumor dormancy through inhibition of angiogenesis.