RESUMO
Exosomes (secreted extracellular vesicles formed in the intracellular vesicular transport system) play a crucial role in distant cell-cell communication. Exosomes transfer active forms of various biomolecules; the molecular composition of the exosomal cargo is a result of targeted selection and depends on the type of producer cells. The mechanisms underlying exosome formation and cargo selection are poorly understood. It is believed that there are several pathways for exosome biogenesis, although the questions about their independence and simultaneous coexistence in the cell still remain open. The least studied topic is the recently discovered mechanism of exosome formation associated with lipid rafts, or membrane lipid microdomains. Here, we present modern concepts and basic hypotheses on the mechanisms of exosome biogenesis and secretion and summarize current data on the involvement of lipid rafts and their constituent molecules in these processes. Special attention is paid to the analysis of possible role in the exosome formation of raft-forming proteins of the SPFH family, components of planar rafts, and caveolin, the main component of caveolae.
Assuntos
Exossomos/metabolismo , Microdomínios da Membrana/metabolismo , Animais , HumanosAssuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologiaAssuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Procedimentos Analíticos em Microchip/métodos , Paclitaxel/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Transdução de SinaisRESUMO
We have previously demonstrated that hamster embryo fibroblasts (HEFs) transformed by Rous Sarcoma virus, Schmidt-Ruppin strain (RSV-SR) are highly resistant to damage by H202 (H2O2R), (in contrast to HEFs transformed spontaneously, or by bovine adenovirus and SV40), while N-ras transfection of RSV-SR transformants leads to suppression of pp6Ov-scr and of H2O2R. In this study we have examined (1) mechanisms of antioxidant activity (AOA) of HEFs transformed by these agents and (2) the possible role of the v-src gene in unusually high AOA of RSV-SR transformants and of activated ras oncogenes in its suppression. All transformants exhibit increased catalase and glutathione peroxidase (GP) activities, while SOD, glutathione and glutathione reductase (GR) were reduced. As compared with other transformants, the significantly higher catalase and the low SOD activities were characteristic of RSV-SR-transformants, while an increase in GP was observed in all types of transformants. Correspondingly, RSV-SR-transformants showed an extremely high H202-catabolizing activity (H2O2CA) and no lipid peroxidation chain reaction (LPCR). N-ras-induced suppression of pp60v-scr of RSV-SR-transformed HEFs coincided with the suppression of catalase, GP, H202 and H202CA. However, suppression of catalase and GP was also observed in N-ras- and Ha-ras-transfected, spontaneously transformed HEFs. Thus, extremely high catalase activity and suppression of LPCR are apparently the main mechanisms of the unusually high H202R of RSV-SR transformants, while its suppression by activated ras oncogenes may also take place in some transformants, free of v-src activity.