RESUMO
Betaine was an endogenous catabolite of choline, which could be isolated from vegetables and marine products. Betaine could promote the metabolism of homocysteine in healthy subjects and was used for hyperlipidemia, coronary atherosclerosis, and fatty liver in clinic. Recent findings shown that Betaine rescued neuronal damage due to homocysteine induced Alzheimer's disease (AD) like pathological cascade, including tau hyperphosphorylation and amyloid-ß (Aß) deposition. Aß was derived from amyloid precursor protein (APP) processing, and was a triggering factor for AD pathological onset. Here, we demonstrated that Betaine reduced Aß levels by altering APP processing in N2a cells stably expressing Swedish mutant of APP. Betaine increased α-secretase activity, but decreased ß-secretase activity. Our data indicate that Betaine might play a protective role in Aß production.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Betaína/farmacologia , Lipotrópicos/farmacologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Homocisteína/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Camundongos , Mutação/genética , Neuroblastoma/patologia , TransfecçãoRESUMO
OBJECTIVE: To isolate exosomes from rabbit aqueous humor and to investigate their immunosuppression function. METHODS: Aqueous humor was collected from 40 New Zealand rabbits and exosomes were isolated by fractional separation and ultracentrifugation methods; the morphology was studied with electron microscopy. The immunosuppressive-related proteins of exosomes were detected with Western blotting; their inhibitory effect on ConA-induced proliferation of T lymphocyte was estimation with CCK-8 cells proliferation assay. RESULTS: Eight milliliters of aqueous humor were collected from 40 New Zealand rabbits and 200 µg exosomes was yielded. Under electron microscope, the exosomes had typical structure of lipid bi-layer with a diameter of 50-100 nm. The results of Western blotting showed that these exosomes expressed Hsp70, CD9 and Alix but not Grp94, presenting a typical exosomes protein profile. Moreover, exosomes expressed high level of TGF-ß and significantly inhibited the proliferation of T lymphocytes. CONCLUSION: Immunosuppressive exosomes can be isolated from rabbit aqueous humor, which may be involved in immunotolerance of the eye.
