INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MKP-1 MODULATES ENDOPLASMIC RETICULUM STRESS EVENTS TRIGGERED BY CISPLATIN IN RENAL TUBULE CELLS
Autor/es:
CABRERA ESCOBAR LUCIANA A; PAZ CRISTINA; ACQUIER ANDREA B; GOROSTIZAGA, ALEJANDRA B; ACQUIER ANDREA B; GOROSTIZAGA, ALEJANDRA B; MENDEZ, CARLOS F; MENDEZ, CARLOS F; CABRERA ESCOBAR LUCIANA A; PAZ CRISTINA
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reuniòn Anual de la Sociedad Argentina de Investigación Clínica; 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
A wide variety of agents induce endoplasmic reticulum stress(RE) in different cell types. RE produces a complex signal transductionpathway known as Unfolding Protein Response that includesactivation of the MAP kinases (MAPKs) ERK1/2, JNK1/2and p38 which have different effects on survival or apoptosis.Stimuli that promote the activation of MAPKs induce the expressionof different members of the family of MAPK phosphatases(MKPs), which promote the inactivation of these kinases. MKP-1is a well characterized member of this family induced by severalstimuli and able to dephosphorylate members of the three MAPKssubgroups. Cisplatin (CPT), a known chemotherapeutic agent, iswidely used as RE inductor. The aim of this work was to determineif MAPK phosphatase 1 (MKP-1) modulates aspects related to REin a human renal proximal tubule-derived cell line (HK-2) expos edto CPT. First, we analyzed MAPKs activation by CPT. Western blotanalysis using specific antibodies against the phosphorylated formsof ERK1/2 showed that 50 mM CPT promotes ERK1/2 activationin a time-dependent manner. The increase was evident after 4 hof stimulation (6-fold) extending to 12 h. We also analyzed MKP-1mRNA levels and we observed that CPT increases mRNA levels in atime- and concentration-dependent manner. In addition, we analyzedthe expression of GRP78, a RE marker involved in cell survival bysemiquantitative RT-PCR. We found that CPT increased GRP78levels reaching a maximum at 6 h (3-fold). PD98059 (50 uM), an inhibitorof ERK1/2 activation, prevented the effect of CPT on GRP78levels, while SB203580 and SP-600125 (JNK and p38 inhibitors,respectively) had no effect, thereby suggesting that GRP78 expressionis modulated by ERK1/2. Moreover, in cells transfected witha construction for transient expression of flag-MKP-1 recombinantprotein, MTT assay showed that transfection with MKP-1 modulatescell viability. Collectively, our data suggest that MKP-1 is inducedby CPT and may contribute to turn off MAPKs-dependent eventstriggered by CPT.