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Doctoral Thesis
DOI
10.11606/T.42.2018.tde-27092010-130755
Document
Author
Full name
Hilton Kenji Takahashi
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Curi, Rui (President)
Abdulkader, Fernando Rodrigues de Moraes
Cirino, Luis Marcelo Inaco
Passarelli, Marisa
Soriano, Francisco Garcia
Title in Portuguese
Mecanismos envolvidos na morte e sobrevivência de linfócitos expostos ao ácido palmítico.
Keywords in Portuguese
Ácidos graxos
Apoptose
Insulina
Linfócitos
Linhagem celular
Metabolismo celular
Abstract in Portuguese
Ácidos graxos podem atuar na apoptose ativando e/ou desativando sinais que regulam este processo. Células Jurkat (linhagem de linfócitos-T) foram tratadas com ácido palmítico (PA) (50, 100 e 150µM) e avaliada a ativação de vias de morte e de sobrevivência. O tratamento com PA induziu apoptose pela ativação da via intrínseca de maneira dose-dependente. A exposição destas células ao PA elevou a expressão do receptor de insulina e de GLUT-4, obtendo-se correlação positiva com a apoptose. O mesmo foi observado em linfócitos humanos expostos ao PA e de linfócitos de ratos em jejum. O tratamento das células Jurkat com insulina após exposição ao PA promoveu a ativação da via de sinalização insulínica. O PA aumentou a captação de glicose, mas observou-se diminuição de sua oxidação e o acúmulo de lípides. Assim, a via de sinalização da insulina e o metabolismo de glicose não oxidativo são estimulados como parte de uma coordenada resposta de sobrevivência de linfócitos expostos ao PA em baixas concentrações, mas em altas concentrações ocorre apoptose.
Title in English
Mechanisms involved in death and survival of lymphocytes exposed to palmitic acid.
Keywords in English
Apoptosis
Cell lineage
Cell metabolism
Fatty acids
Insulin
Lymphocytes
Abstract in English
Fatty acids affect apoptosis pathway activating or deactivating signals that regulate this process. Jurkat cells (T-lymphocyte lineage) were treated with sub-lethal concentrations of palmitic acid (PA) (50, 100 e 150µM) and the cell death and survival signaling pathways were investigated. PA induced apoptosis in a dose dependent manner activating the intrinsic pathway. Jurkat cells exposed to PA showed increased insulin receptor and GLUT-4 expression and a positive correlation with apoptosis was obtained. Similar effect was observed in human lymphocytes exposed to PA and lymphocytes from fasted rats. Insulin treatment of Jurkat cells after PA exposure promoted the activation of the insulin signaling pathway. Glucose uptake was increased in the presence of PA, however, its oxidation was diminished and ncreased of lipids accumulation. Therefore, insulin signaling and non oxidative glucose metabolism are stimulated as a part of a coordinated response to survival of lymphocytes exposed to low concentration of PA but in high concentration it induces apoptosis.
 
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Publishing Date
2018-12-05
 
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