MORTE CELULAR 18/06/2015 - WordPress.com · 6/18/2015 · MORTE CELULAR 18/06/2015. apoptosis cell...
Transcript of MORTE CELULAR 18/06/2015 - WordPress.com · 6/18/2015 · MORTE CELULAR 18/06/2015. apoptosis cell...
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MORTE CELULAR18/06/2015
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cell deathapoptosis
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De acordo com o NCCD de 2015...
Acidental cel ldeath (ACD) – imprevinível
Regulated cell death (RCD) – previnível, pode ser modulada
Pprogrammed cell death (PCD) – “completamente fisiológico”
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Hennighausen and Groner, 2003
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Seleção de células no sistema imune
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A apoptose depende de proteólise mediada por caspases
Caspases: enzimas responsáveis pela proteólise
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Figure 18-5a Molecular Biology of the Cell (© Garland Science 2008)
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Figure 18-5b Molecular Biology of the Cell (© Garland Science 2008)
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Há 2 vias de sinalizaçãoque ativam as caspases
• Via extrínsica
• Via intrínsica
Cada uma dessas usa suas próprias caspases iniciadoras e complexos de ativação
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Via extrínsica
DISC = death-induced signaling complex
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Apaf1 = apoptotic protease activating factor-1CARD=caspase recruitment domain
Via intrínsica
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controlam a liberação de citocromo C
anti-apoptóticos – bloqueiam a liberação de cyt C
pró-apoptóticos – estimulam a liberação de cyt C
Família Bcl2
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Membros da família Bcl2
BH = Bcl-2 homology
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Fonte de confusão...
A família Bcl2 inclui membros PRÓ e ANTI apoptóticos
SÓ QUE um dos membros se chama Bcl2, esse é ANTI-apoptótico
Por isso a expressão pro-apoptotic Bcl2 proteins é uma armadilha!
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Como os pró-apoptóticos atuam
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Se um ANTI-apoptótico estiver ativo, esse inibi os PRÓ-apoptóticos
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Figure 18-11b Molecular Biology of the Cell (© Garland Science 2008)
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• A via extrínsica pode ativar a intrínsica para aamplificar a cascata de caspases. Isso é feito através da BH3 Bid
• Caspase 8 →clivagem de Bid →tBid trasnloca-se para a mitocôndria e induz agregação dos BH123
• Bim, Bid e Puma são capazes de inibir TODOS os membros ANTI-apoptóticos
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IAPs e anti-IAPs
• IAP = inhibitors of apoptosis
• “Equivalentes” às proteínas Bcl2 em mamíferos
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IAP inibe ativaçãoespontânea de caspases
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sobreviva
divida-se
diferencie
morra
Lembrando da aula de sinalização..
Fatores de Sobrevivência
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Células competem por fatores de crescimento no adulto e no desenvolvimento
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Sinalização dos fatores de sobrevivência segue a mesma regra ....
molécula extracelular
receptor
Moléculas de sinalização intracelular
proteínas efetoras
fator de sobrevivência
Proteínas Bcl2a
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Resposta rápida ou lenta
Crescimentodivisão
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