Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients
Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV). This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evalu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Universidade de São Paulo
2011-12-01
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| Series: | Brazilian Journal of Pharmaceutical Sciences |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502011000400025 |
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| author | Elainy Patricia Lino Gasparotto Raquel Tognon Aline Fernanda Ferreira Gislane Lelis Vilela Oliveira Patrícia Vianna Bonini Palma Maria Aparecida Zanichelli Elizabeth Xisto Souto Carlos Eduardo Engel Velano Belinda Pinto Simões Rita de Cassia Viu Carrara Simone Kashima Dimas Tadeu Covas Fabíola Attie de Castro Ana Maria de Souza |
| author_facet | Elainy Patricia Lino Gasparotto Raquel Tognon Aline Fernanda Ferreira Gislane Lelis Vilela Oliveira Patrícia Vianna Bonini Palma Maria Aparecida Zanichelli Elizabeth Xisto Souto Carlos Eduardo Engel Velano Belinda Pinto Simões Rita de Cassia Viu Carrara Simone Kashima Dimas Tadeu Covas Fabíola Attie de Castro Ana Maria de Souza |
| author_sort | Elainy Patricia Lino Gasparotto |
| collection | DOAJ |
| description | Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV). This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005). CD34+ cells from PV patients presented higher levels of A1 and Mcl-1 expression (median: 22.6 and 5.2, respectively) in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020); while Bcl-2 and Bcl-xL expression decreased in PV patients (0.18 and 1.19) compared with controls (1.39 and 2.01, p=0.006 and p=0.020). CD34+ cells in PV patients showed an elevated Bid expression (14.4) in comparison with healthy subjects (1.0; p=0.002). Patients' leukocytes showed an A1 augmentation (7.41, p=0.001) and a reduced expression of Bax (0.19; p=0.040) and Bad (0.2; p=0.030). There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis.<br>A desregulação da apoptose parece participar da fisiopatologia da policitemia vera (PV). Este estudo avaliou a expressão das moléculas da família Bcl-2 em células hematopoéticas CD34 + e leucócitos de 12 pacientes com PV. Foram realizados: a quantificação da expressão gênica por PCR em tempo real utilizando kit Sybrgreen Quantitect, avaliação da expressão de proteínas por western-blot e detecção da mutação JAK2 V617F segundo Baxter et al. (2005). Células CD34 + dos pacientes com PV apresentaram maior expressão de A1 e Mcl-1 (mediana: 22,6 e 5,2, respectivamente) em comparação com controles (0,9 e 0,5, p = 0,004 e p = 0,020) e expressão de Bcl-2 e Bcl-xL diminuída nestes pacientes (0,18 e 1,19) em relação aos controles (1,39 e 2,01, p = 0,006 e p = 0,020). Células CD34 + dos pacientes com PV mostraram expressão elevada de bid (14,4) em comparação aos controles (1,0; p = 0,002). Leucócitos dos pacientes mostraram aumento de A1 (7,41, p = 0,001) e expressão reduzida do Bax (0,19; p = 0,04) e Bad (0,2; p = 0,030). Não houve correlação entre percentagem de alelos JAK2 V617F mutados e expressão molecular. Pacientes com PV apresentaram alterações na expressão de moléculas Bcl-2 que podem interferir no controle da apoptose e contribuir para a patogênese da doença. |
| first_indexed | 2024-12-14T06:28:31Z |
| format | Article |
| id | doaj.art-08acecd847414973a5ab5c97ae0eb57c |
| institution | Directory Open Access Journal |
| issn | 1984-8250 2175-9790 |
| language | English |
| last_indexed | 2024-12-14T06:28:31Z |
| publishDate | 2011-12-01 |
| publisher | Universidade de São Paulo |
| record_format | Article |
| series | Brazilian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-08acecd847414973a5ab5c97ae0eb57c2022-12-21T23:13:36ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences1984-82502175-97902011-12-0147487388610.1590/S1984-82502011000400025Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patientsElainy Patricia Lino GasparottoRaquel TognonAline Fernanda FerreiraGislane Lelis Vilela OliveiraPatrícia Vianna Bonini PalmaMaria Aparecida ZanichelliElizabeth Xisto SoutoCarlos Eduardo Engel VelanoBelinda Pinto SimõesRita de Cassia Viu CarraraSimone KashimaDimas Tadeu CovasFabíola Attie de CastroAna Maria de SouzaApoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV). This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005). CD34+ cells from PV patients presented higher levels of A1 and Mcl-1 expression (median: 22.6 and 5.2, respectively) in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020); while Bcl-2 and Bcl-xL expression decreased in PV patients (0.18 and 1.19) compared with controls (1.39 and 2.01, p=0.006 and p=0.020). CD34+ cells in PV patients showed an elevated Bid expression (14.4) in comparison with healthy subjects (1.0; p=0.002). Patients' leukocytes showed an A1 augmentation (7.41, p=0.001) and a reduced expression of Bax (0.19; p=0.040) and Bad (0.2; p=0.030). There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis.<br>A desregulação da apoptose parece participar da fisiopatologia da policitemia vera (PV). Este estudo avaliou a expressão das moléculas da família Bcl-2 em células hematopoéticas CD34 + e leucócitos de 12 pacientes com PV. Foram realizados: a quantificação da expressão gênica por PCR em tempo real utilizando kit Sybrgreen Quantitect, avaliação da expressão de proteínas por western-blot e detecção da mutação JAK2 V617F segundo Baxter et al. (2005). Células CD34 + dos pacientes com PV apresentaram maior expressão de A1 e Mcl-1 (mediana: 22,6 e 5,2, respectivamente) em comparação com controles (0,9 e 0,5, p = 0,004 e p = 0,020) e expressão de Bcl-2 e Bcl-xL diminuída nestes pacientes (0,18 e 1,19) em relação aos controles (1,39 e 2,01, p = 0,006 e p = 0,020). Células CD34 + dos pacientes com PV mostraram expressão elevada de bid (14,4) em comparação aos controles (1,0; p = 0,002). Leucócitos dos pacientes mostraram aumento de A1 (7,41, p = 0,001) e expressão reduzida do Bax (0,19; p = 0,04) e Bad (0,2; p = 0,030). Não houve correlação entre percentagem de alelos JAK2 V617F mutados e expressão molecular. Pacientes com PV apresentaram alterações na expressão de moléculas Bcl-2 que podem interferir no controle da apoptose e contribuir para a patogênese da doença.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502011000400025Policitemia veraMutação gênicaExpressão gênicaApoptoseMembros da Família Bcl-2Polycythemia veraGene mutationGene expressionApoptosisBcl-2 family members |
| spellingShingle | Elainy Patricia Lino Gasparotto Raquel Tognon Aline Fernanda Ferreira Gislane Lelis Vilela Oliveira Patrícia Vianna Bonini Palma Maria Aparecida Zanichelli Elizabeth Xisto Souto Carlos Eduardo Engel Velano Belinda Pinto Simões Rita de Cassia Viu Carrara Simone Kashima Dimas Tadeu Covas Fabíola Attie de Castro Ana Maria de Souza Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients Brazilian Journal of Pharmaceutical Sciences Policitemia vera Mutação gênica Expressão gênica Apoptose Membros da Família Bcl-2 Polycythemia vera Gene mutation Gene expression Apoptosis Bcl-2 family members |
| title | Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients |
| title_full | Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients |
| title_fullStr | Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients |
| title_full_unstemmed | Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients |
| title_short | Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients |
| title_sort | deregulated expression of a1 bcl 2 bcl xl and mcl 1 antiapoptotic proteins and bid bad and bax proapoptotic genes in polycythemia vera patients |
| topic | Policitemia vera Mutação gênica Expressão gênica Apoptose Membros da Família Bcl-2 Polycythemia vera Gene mutation Gene expression Apoptosis Bcl-2 family members |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502011000400025 |
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