RESUMO
A 24-amino acid leader peptide of a new human recombinant manganese superoxide dismutase can enter cells and carry molecules. Here, we demonstrated that six of the 24 amino acids penetrate cells through a particular gate represented by a specific amino acid sequence of the oestrogen receptor (ER). We analysed the internalization of the synthetic hexapeptide and the cytotoxic activity of the hexapeptide conjugated to cisplatin on a cell line panel. In most cell lines, the hexapeptide delivered an amount of cisplatin that was 2 to 8 times greater than that released by cisplatin when the drug was used alone. This increased delivery increases the therapeutic index of cisplatin and reduces side effects caused by a high dosage or long-term treatment times. We may consider this hexapeptide a new molecular carrier to deliver molecules with therapeutic activity into ER(+) cells for diagnostic purposes and clinical or immune therapy.
Assuntos
Portadores de Fármacos/química , Fragmentos de Peptídeos/química , Sequência de Aminoácidos , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/química , Cisplatino/metabolismo , Cisplatino/farmacologia , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Retículo Endoplasmático/metabolismo , Fluoresceína/química , Fluoresceína/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Humanos , Concentração Inibidora 50 , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Sinais Direcionadores de Proteínas , Receptores de Estrogênio/metabolismo , Proteínas Recombinantes/química , Superóxido Dismutase/químicaRESUMO
In humans red blood cells live on average of 120 days. Senescent erythrocytes are removed from circulation by macrophages; this process, called erythrophagocytosis (EPC), takes place mainly in the liver but also in the bone marrow. We studied this process in loggerhead turtles Caretta caretta, inhabiting the Mediterranean Sea. Leukocytes of reptiles include heterophils, eosinophils, lymphocytes, basophils, thrombocytes, monocytes, and of these heterophils and monocytes represent the main phagocytic cells. The aim of this study was to investigate the blood of C. caretta specimens and to observe, in the blood smears, heterophils phagocytizing erythrocytes. The phagocytizing cells were also identified by cytochemical reactions. Furthermore some examples of tear-shaped erythrocytes (dacrocytes) were observed. A mechanism presuming a causative link between erythrophagocytosis and teardrop-erythrocyte detection have been proposed to explain this seemingly general pattern of all specimens both wild and housed.