Prolactina induz aumento na expressão das proteinas SNARE e da sinaptotagmina 4 em ilhotas de ratos
Daniel Andrade da Cunha
DISSERTAÇÃO
Português
(Broch.)
T/UNICAMP C914p
Campinas, SP : [s.n.], 2004.
54f. : il.
Orientador: Antonio Carlos Boschero
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Resumo: Muitas proteínas estão envolvidas no processo de extrusão de grânulos e fusão de membranas nas células ß pancreáticas, e entre estas se destacam as proteínas da família SNARE, composta pela sintaxina, VAMP, SNAP-25 e as sinaptotagminas. Durante a prenhez e o período pós-natal, a prolactina...
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Resumo: Muitas proteínas estão envolvidas no processo de extrusão de grânulos e fusão de membranas nas células ß pancreáticas, e entre estas se destacam as proteínas da família SNARE, composta pela sintaxina, VAMP, SNAP-25 e as sinaptotagminas. Durante a prenhez e o período pós-natal, a prolactina (PRL) e os lactogênios placentários induzem a maturação do processo secretório nas ilhotas pancreáticas por um mecanismo que não está totalmente conhecido. Assim, o objetivo deste trabalho foi analisar se o aumento na resposta secretória frente à glicose observado durante a prenhez envolve alterações na expressão das proteínas SNARE e das sinaptotagminas 1 e 4. Observamos aumento na expressão gênica e protéica da sintaxina 1A, SNAP-25, VAMP-2 e da sinaptotagmina 4 nas ilhotas de neonatos (1 ¿ 2 dias de vida) tratadas com PRL. Demonstramos também que ilhotas de ratas prenhes (17 ¿ 18 dias após cópula) apresentam maior expressão da sintaxina 1A, SNAP-25 e sinaptotagmina 4 que ilhotas controle. Além disso, a inibição das vias da PI3-cinase pela wortmanina ou da MAP-cinase pelo PD098059, não alterou a transcrição destes genes. Desta forma, podemos concluir que prolactina modula a expressão gênica e protéica de parte dos componentes ligados aos passos finais da extrusão dos grânulos de insulina e que este efeito não é mediado pelas vias da PI3- ou da MAPcinase
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Abstract: The soluble N-ethylmaleimide-sensitive factor attached protein receptor (SNARE) molecules SNAP-25, syntaxin and VAMP-2 as well as synaptotagmins participate in the
extrusion of insulin containing granules in pancreatic ß-cells. During pregnancy and the perinatal periods of life, prolactin... Ver mais Abstract: The soluble N-ethylmaleimide-sensitive factor attached protein receptor (SNARE) molecules SNAP-25, syntaxin and VAMP-2 as well as synaptotagmins participate in the
extrusion of insulin containing granules in pancreatic ß-cells. During pregnancy and the perinatal periods of life, prolactin (PRL) and other lactogenic substances induce maturation of the stimulus-secretion coupling in the pancreatic islets by a mechanism that is still unclear. In the present study, we investigated whether the improvement in the secretory response to glucose during those periods involves alteration in the expression of syntaxin 1A, SNAP-25, VAMP-2 and synaptotagmins 1 and 4. In islets from pregnant rats (17th ¿ 18th days of pregnancy) and islets from neonatal rats (1-2 days old) treated with PRL for five days, the expression of syntaxin, SNAP-25 and synaptotagmin 4 genes and their encoded proteins was increased compared with controls. VAMP-2 gene and protein was increased in PRL treated-islets from neonatal rats but not in islets from pregnants rats. Wortmannin, a PI3-kinase inhibitor, and PD098059 (PD), a MAP-kinase inhibitor, failed to abrogate the effect of treatment with PRL on the expression of the above proteins. In conclusion, these data indicate that PRL modulates the final steps of insulin secretion by increasing the expression of proteins involved in membrane fusion. These experiments also indicate that effects of PRL occur mainly through a signaling cascade distinct from the PI3-kinase or MAP-kinase pathways Ver menos
extrusion of insulin containing granules in pancreatic ß-cells. During pregnancy and the perinatal periods of life, prolactin... Ver mais Abstract: The soluble N-ethylmaleimide-sensitive factor attached protein receptor (SNARE) molecules SNAP-25, syntaxin and VAMP-2 as well as synaptotagmins participate in the
extrusion of insulin containing granules in pancreatic ß-cells. During pregnancy and the perinatal periods of life, prolactin (PRL) and other lactogenic substances induce maturation of the stimulus-secretion coupling in the pancreatic islets by a mechanism that is still unclear. In the present study, we investigated whether the improvement in the secretory response to glucose during those periods involves alteration in the expression of syntaxin 1A, SNAP-25, VAMP-2 and synaptotagmins 1 and 4. In islets from pregnant rats (17th ¿ 18th days of pregnancy) and islets from neonatal rats (1-2 days old) treated with PRL for five days, the expression of syntaxin, SNAP-25 and synaptotagmin 4 genes and their encoded proteins was increased compared with controls. VAMP-2 gene and protein was increased in PRL treated-islets from neonatal rats but not in islets from pregnants rats. Wortmannin, a PI3-kinase inhibitor, and PD098059 (PD), a MAP-kinase inhibitor, failed to abrogate the effect of treatment with PRL on the expression of the above proteins. In conclusion, these data indicate that PRL modulates the final steps of insulin secretion by increasing the expression of proteins involved in membrane fusion. These experiments also indicate that effects of PRL occur mainly through a signaling cascade distinct from the PI3-kinase or MAP-kinase pathways Ver menos
Prolactina induz aumento na expressão das proteinas SNARE e da sinaptotagmina 4 em ilhotas de ratos
Daniel Andrade da Cunha
Prolactina induz aumento na expressão das proteinas SNARE e da sinaptotagmina 4 em ilhotas de ratos
Daniel Andrade da Cunha
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