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Non-neuronal muscarinic receptor activation prevents apoptosis of endothelial cells induced by homocysteine / 中国应用生理学杂志
Chinese Journal of Applied Physiology ; (6): 565-572, 2013.
Artigo em Inglês | WPRIM | ID: wpr-235313
ABSTRACT
<p><b>OBJECTIVE</b>Endothelial apoptosis plays an important role in the initiation of atherosclerosis. It would be useful to clarify whether activation of non-neuronal muscarinic receptor (NNMR) could prevent endothelial apoptosis and atherosclerosis. We investigated the effects of NNMR activation on regulating rat aortic endothelial cells (RAECs) apoptosis induced by homocysteine, an independent risk factor of atherosclerosis, and further studied its molecular mechanism.</p><p><b>METHODS</b>RAECs were incubated using homocysteine at the concentration of 2.7 mmol/L for 36 h. RAECs were also pre-treated with carbachol or arecoline to examine their effects. RT-PCR was used to assess changes in the gene expression related to cell apoptosis.</p><p><b>RESULTS</b>Incubation of RAECs with homocysteine at the concentration of 2.7 mmol/L resulted in morphologic changes, such as cellular shrinkage, membrane blebbing, chromatin condensation and margination. These could be attenuated by pretreatment with carbachol and arecoline at the concentration of 10 micromol/L for 12 h. Homocysteine induced apoptosis in RAECs and the molecular mechanisms were associated with the regulation of fas, fas-L and caspase-8 in the death receptor pathway, bcl-2, bcl-xL and bax in the mitochondrial pathway, caspase-12 in the endoplasmic reticulum pathway and caspase-3, caspase-6 and p53 as downstream effectors. Carbachol and arecoline attenuated the effects of homocysteine on genes in the death receptor pathway, in the mitochondrial pathway and in the downstream pathway. Atropine could reverse all of the effects of arecoline.</p><p><b>CONCLUSION</b>Activation of NNMR by carbacol and arecoline inhibits homocysteine-induced endothelial cell apoptosis mainly through regulation of death receptor pathway, mitochondrial pathway and downstream effectors.</p>
Assuntos
Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Aorta / Arecolina / Carbacol / Ciclo Celular / Receptores Muscarínicos / Apoptose / Biologia Celular / Células Endoteliais / Retículo Endoplasmático / Proteínas Reguladoras de Apoptose Tipo de estudo: Fatores de risco Limite: Animais Idioma: Inglês Revista: Chinese Journal of Applied Physiology Ano de publicação: 2013 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Aorta / Arecolina / Carbacol / Ciclo Celular / Receptores Muscarínicos / Apoptose / Biologia Celular / Células Endoteliais / Retículo Endoplasmático / Proteínas Reguladoras de Apoptose Tipo de estudo: Fatores de risco Limite: Animais Idioma: Inglês Revista: Chinese Journal of Applied Physiology Ano de publicação: 2013 Tipo de documento: Artigo