Regulation of the drug transporter abcb1 by atorvastatin in a human hepatoma cell line (2006)
- Authors:
- USP affiliated authors: CURI, RUI - ICB ; BRITTO, LUIZ ROBERTO GIORGETTI DE - ICB
- Unidade: ICB
- Assunto: FISIOLOGIA
- Language: Português
- Abstract: Objetivo: The effects of atorvastatin, an HMG-CoA reductase inhibitor, on the expression and activity of the drug transporter ABCB1 in human hepatoma cell line were examined. Métodos e Resultados: Treatment of HepG2 with 0-20µM atorvastatin for 24h had no effect on the viability, DNA fragmentation or proliferation of the cells. Immunohistochemical analysis with the 17F9 monoclonal antibody revealed that ABCB1 is located at the apical membrane of the bile canaliculi. Atorvastatin at 10?M and 20?M up-regulated ABCB1 expression resulting in a significant 1.4-fold increase of the protein levels (Fluorescence Intensity Mean ± SEM; n = 4: control: 34 ± 2; 10 ?M: 47 ± 4, p< 0.05; 20 ?M: 49 ± 5, p< 0.01). Results from TaqMan® Real-time PCR demonstrated that ABCB1 mRNA expression was reduced in at least 65% after 24-h treatment with atorvastatin (Relative mRNA expression Mean ± SD; Control: 0.0017 ± 0.0007; 10 µM: 0.0006 ± 0.0003 p= 0.043; 20µM: 0.00041 ± 0.00007; p= 0.028). This decrease in mRNA expression was associated with a significant 41% reduction in ABCB1-mediated efflux of Rh123 in HepG2 after 20 µM atorvastatin treatment (p < 0.01). A significant positive correlation was found between ABCB1 mRNA levels and ABCB1 activity (r = 0.98; p= 0.0062). Conclusões: Our data suggest that high concentration of atorvastatin leads to decreased ABCB1 function and modulates ABCB1 synthesis in HepG2 cells. As ABCB1 appears to play a role in cellular protection as well as insecretion and/or disposition, thus, inhibition of ABCB1 synthesis may result in resistance to atorvastatin and may raise its plasma concentrations causing adverse effects
- Imprenta:
- Publisher: Federação de Sociedades de Biologia Experimental
- Publisher place: Águas de Lindóia
- Date published: 2006
- Source:
- Título do periódico: Programa e resumos
- Conference titles: Reunião Anual da Federação de Sociedades de Biologia Experimental - FESBE
-
ABNT
RODRIGUES, Alice Cristina et al. Regulation of the drug transporter abcb1 by atorvastatin in a human hepatoma cell line. 2006, Anais.. Águas de Lindóia: Federação de Sociedades de Biologia Experimental, 2006. . Acesso em: 19 abr. 2024. -
APA
Rodrigues, A. C., Curi, R., Britto, L. R. G. de, Rebecchi, I. M. M., Hirata, M. H., & Hirata, R. D. C. (2006). Regulation of the drug transporter abcb1 by atorvastatin in a human hepatoma cell line. In Programa e resumos. Águas de Lindóia: Federação de Sociedades de Biologia Experimental. -
NLM
Rodrigues AC, Curi R, Britto LRG de, Rebecchi IMM, Hirata MH, Hirata RDC. Regulation of the drug transporter abcb1 by atorvastatin in a human hepatoma cell line. Programa e resumos. 2006 ;[citado 2024 abr. 19 ] -
Vancouver
Rodrigues AC, Curi R, Britto LRG de, Rebecchi IMM, Hirata MH, Hirata RDC. Regulation of the drug transporter abcb1 by atorvastatin in a human hepatoma cell line. Programa e resumos. 2006 ;[citado 2024 abr. 19 ] - Efeitos da aplicação de cloreto de potássio sobre a expressão dos subtipos de receptores muscarínicos da acetilcolina no córtex de ratos
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