IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Subcellular localization of FKBP51 is modified in a redox-sensitive manner
Autor/es:
DE LEO S.A.; GALLO L.; ERLEJMAN A.G.; GALIGNIANA M.D.
Lugar:
Buenos Aires
Reunión:
Congreso; VIII Meeting of the Society for Free Radical Biology and Medicine-South American Group; 2013
Institución organizadora:
Free Radical Biology and Medicine-South American Group
Resumen:
The immunophilin FKBP51 was first described as a cytosolic regulator of steroid receptors. Recently, we demonstrated that FKBP51 is also mitochondrial and translocates to the nucleus upon the onset of oxidative-stress. In this study, we first compared the subcellular localization of FKBP51 in normal and cancer cell types (HeLa, U2OS, MCF7, Caco-2, HepG-2, T47D) by confocal microscopy and found that, in contrast to the mitochondrial localization exhibited by normal cells, FKBP51 shows preponderant nuclear (and nucleolar) localization. This paralleled increased H2DCFDA (2´,7´-dichlorodihydrofluorescein-diacetate) cell staining, suggesting a dependence with the redox-status of the cell. Accordingly, glutathione treatment reversed FKBP51 localization. In HEK293-51 cells (an FKBP51 overexpressing cell line), the nuclear accumulation of the immunophilin was greater than in wild-type cells (WT). Even though H2O2 (100mM for 24h) diminished the number of viable cells (MTT-viability test), the HEK293-51 cell line showed significantly greater viability (70% vs. 60% WT). Overexpression of FKBP52 (a natural FKBP51 competitor) decreased cell viability to 34% in response to H2O2. We conclude that: a)-FKBP51 subcellular localization depends on the redox-status of the cell, b)-its overexpression protects cells against the deleterious action of oxidative stress, and c)-the FKBP51/FKBP52 expression balance could regulate cell survival in response to oxidative damage.