Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1

Background: Several polymorphisms of the CTLA4 gene have been associated with autoimmune diseases. The activation of induced cell death is the major event and caspase 3 represents the main protein for the apoptotic machinery, especially in lymphocytes. Aim: To correlate CTLA4 polymorphisms with casp...

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Autores principales:	Angel B,Bárbara, Codner,Ethel, Arredondo O,Miguel, Salas P,Francisca, Pizarro A,Carolina, Pérez B,Francisco
Lenguaje:	Spanish / Castilian
Publicado:	Sociedad Médica de Santiago 2012
Materias:	Apoptosis Caspase 3 Diabetes Melllitus type 1
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872012000900002
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spelling	oai:scielo:S0034-988720120009000022013-01-02Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1Angel B,BárbaraCodner,EthelArredondo O,MiguelSalas P,FranciscaPizarro A,CarolinaPérez B,Francisco Apoptosis Caspase 3 Diabetes Melllitus type 1 Background: Several polymorphisms of the CTLA4 gene have been associated with autoimmune diseases. The activation of induced cell death is the major event and caspase 3 represents the main protein for the apoptotic machinery, especially in lymphocytes. Aim: To correlate CTLA4 polymorphisms with caspase 3 expression in peripheral blood mononuclear cells (PBMC) simulating in vitro the glucose effect. Material and Methods: CTLA4 polymorphisms were determined by restriction fragment length polymorphisms (RFLPs). PBMC from 21 patients with type 1 diabetes aged 8.5 ± 4.3 years and 21 healthy subjects aged 18.3 ± 1.8 years, were stimulated under normal (5 mM) and toxic (14 mM) glucose conditions to assess its effect on the expression and activity of caspase 3. Relative abundance of caspase 3 mRNA was measured by semi quantitative RT-PCR and its activity, by a colorimetric assay. Results: When stimulated with 14mM glucose, PBMC of G allele carriers with type 1 diabetes had significantly lower relative mRNA abundance of caspase 3 (median value = 0.12, range 0.01-0.70 AU) compared with non-carriers (median value = 0.81, range 0.06-1.09 AU). When the incubation was carried out with the lower glucose concentration, a similar profile of caspase 3 activity was observed in diabetic patients carrying G allele (median value = 0.57, range 0.13-1.20 AU) as compared with non-carriers (median value = 0.89, range 0.14-5.50 AU). No significant changes after stimulating with glucose, were observed in PBMCs of the control group. Conclusions: PBMC of recently diagnosed patients with T1D, carrying the G allele in + 49A/G polymorphisms of CTLA4, have a decreased expression and activity of caspase 3.info:eu-repo/semantics/openAccessSociedad Médica de SantiagoRevista médica de Chile v.140 n.9 20122012-09-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872012000900002es10.4067/S0034-98872012000900002
institution	Scielo Chile
collection	Scielo Chile
language	Spanish / Castilian
topic	Apoptosis Caspase 3 Diabetes Melllitus type 1
spellingShingle	Apoptosis Caspase 3 Diabetes Melllitus type 1 Angel B,Bárbara Codner,Ethel Arredondo O,Miguel Salas P,Francisca Pizarro A,Carolina Pérez B,Francisco Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1
description	Background: Several polymorphisms of the CTLA4 gene have been associated with autoimmune diseases. The activation of induced cell death is the major event and caspase 3 represents the main protein for the apoptotic machinery, especially in lymphocytes. Aim: To correlate CTLA4 polymorphisms with caspase 3 expression in peripheral blood mononuclear cells (PBMC) simulating in vitro the glucose effect. Material and Methods: CTLA4 polymorphisms were determined by restriction fragment length polymorphisms (RFLPs). PBMC from 21 patients with type 1 diabetes aged 8.5 ± 4.3 years and 21 healthy subjects aged 18.3 ± 1.8 years, were stimulated under normal (5 mM) and toxic (14 mM) glucose conditions to assess its effect on the expression and activity of caspase 3. Relative abundance of caspase 3 mRNA was measured by semi quantitative RT-PCR and its activity, by a colorimetric assay. Results: When stimulated with 14mM glucose, PBMC of G allele carriers with type 1 diabetes had significantly lower relative mRNA abundance of caspase 3 (median value = 0.12, range 0.01-0.70 AU) compared with non-carriers (median value = 0.81, range 0.06-1.09 AU). When the incubation was carried out with the lower glucose concentration, a similar profile of caspase 3 activity was observed in diabetic patients carrying G allele (median value = 0.57, range 0.13-1.20 AU) as compared with non-carriers (median value = 0.89, range 0.14-5.50 AU). No significant changes after stimulating with glucose, were observed in PBMCs of the control group. Conclusions: PBMC of recently diagnosed patients with T1D, carrying the G allele in + 49A/G polymorphisms of CTLA4, have a decreased expression and activity of caspase 3.
author	Angel B,Bárbara Codner,Ethel Arredondo O,Miguel Salas P,Francisca Pizarro A,Carolina Pérez B,Francisco
author_facet	Angel B,Bárbara Codner,Ethel Arredondo O,Miguel Salas P,Francisca Pizarro A,Carolina Pérez B,Francisco
author_sort	Angel B,Bárbara
title	Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1
title_short	Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1
title_full	Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1
title_fullStr	Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1
title_full_unstemmed	Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1
title_sort	expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito t-citotóxico (ctla4) en pacientes chilenos con diabetes tipo 1
publisher	Sociedad Médica de Santiago
publishDate	2012
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872012000900002
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Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1

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