RESUMO
Previously, we have demonstrated that basic fibroblast growth factor (bFGF) decreases elastin gene transcription in confluent rat lung fibroblasts via the binding of a Fra-1-c-Jun heterodimer to an activator protein-1-cAMP response element in the distal region of the elastin promoter. In the present study, we show that bFGF activates the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2, resulting in the translocation of phosphorylated extracellular signal-regulated kinase 1/2 into the nucleus followed by increased binding of Elk-1 to the serum response element of the c-Fos promoter, transient induction of c-Fos mRNA, and sustained induction of Fra-1 mRNA. The addition of PD-98059, an inhibitor of mitogen-activated protein kinase kinase, abrogates the bFGF-dependent repression of elastin mRNA expression. Comparative analyses of confluent and subconfluent fibroblast cultures reveal significant differences in elastin mRNA levels and activator protein-1 protein factors involved in the regulation of elastin transcription. These findings suggest that bFGF modulates specific cellular events that are dependent on the state of the cell and provide a rationale for the differential responses that can be expected in development and injury or repair situations.
Assuntos
Proteínas de Ligação a DNA , Elastina/genética , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fibroblastos/enzimologia , Pulmão/citologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fatores de Transcrição , Animais , Elastina/metabolismo , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica/efeitos dos fármacos , Proteínas Elk-1 do Domínio etsRESUMO
Primer residue typically contains some combination of lead, antimony, or barium, whereas bullet residue from nonjacketed bullets is 70-100% lead. The amount of lead particles produced by low-velocity bullets (projectile residue) may be exceedingly high. Copper- or brass-coated bullets generate an admixture of lead and copper particles whereas jacketed and semijacketed bullets produce the least amount of lead particles and only a small amount of copper-containing residue. We recently studied a suicidal contact small-caliber gunshot wound with an unusual amount of bullet residue deposited on the epidermal margins and within the wound track. The entrance wound was encircled by radiopaque particulate material visible on the postmortem radiograph. Soft radiography delineated the material to the wound track and adjacent epidermis. Scanning electron microscopy with energy-dispersive analysis of x-rays identified the principle element as lead.
