INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ALBUMIN OVERLOAD UP-REGULATES MKP-1 IN RENALTUBULAR CELLS
Autor/es:
ALEJANDRA B GOROSTIZAGA; NATALIA V GOMEZ; ANDREA ACQUIER; MM MORI SEQUEIROS GARCÍA; SOL RECA; CARLOS F MENDEZ; CRISTINA PAZ
Lugar:
Mendoza
Reunión:
Congreso; XLVII Reunión Anual - Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2012
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
In renal tubular cells, albumin overload promotes both the transient activation of MAP kinases (ERK1/2, JNK1/2 and p38) and reticulum stress (RS). MAP kinase phosphatases (MKPs) areinduced by several stimuli to inactivate MAPKs. MKP-1 is a nuclear MKP that dephosphorylates all MAPKs. Here we analyzed the effect of albumin (BSA, 20 mg/ml) in a proximal tubulederivedcell line of opossum (Didelphis virginiana ) origin (OK cells). Western blot analysis showed that BSA promoted MKP-1 accumulation after 1 h of stimulation (2-fold). Since the MKP-1 genome sequence of opossum is not completely characterized, we designed oligonucleotides based on the sequence described for the highly related Monodelphis sp , to isolate the MKP-1 cDNA from OK cells by RT-PCR. Sequence homology between species of the isolated cDNA was 98%. Next, using specific oligonucleotides, we evaluated the effect of BSA on MKP-1 mRNA levels. BSAtransiently increased mRNA levels (2-fold after 1h), an effect blocked by actinomycin D, which suggests that BSA activates MKP-1 gene transcription. BSA also increased mRNA levels ofGRP78 protein, an RS marker, and an inhibitor of ERK1/2 activation (PD98059, 50 μM),  prevented this effect. Collectively, our data indicate that MKP-1 is induced by BSA at a transcriptional level and suggest that it may contribute to turn off ERK-dependent events triggered by BSA.