DMPO AFFECTS STRESS RESPONSE IN LPS-PRIMED CELLS

MUNOZ MD; SANDRA E. GOMEZ-MEJIBA; DARIO C. RAMIREZ

POTRERO DE LOS FUNES

Congreso; SCB 2012; 2012

SBCUYO

DMPO AFFECTS STRESS RESPONSE IN LPS-PRIMMED CELLS.(POSTER) Zhai Z, Gomez-Mejiba SE, Ramirez DC. Laboratorio de Medicina Experimental y Terapéutica. IMIBIO-SL-COJICET-UJSL, San Luis The nitrone spin trap 5,5-dimethyl-1-pyrroline J-oxide (DMPO) is commonly used to study free radicals. Due to its free radical trapping properties, DMPO is thought to reduce free radial-mediated oxidative damage and other related cellular responses. Previously, we have shown that DMPO interferes with NF-kB inflammatory signaling triggered by lipopolysaccharide (LPS) in macrophages. This interference also resulted in trapping of protein radicals in specific cell compartments. The purpose of this study was to assess the effect of DMPO on LPS-induced inflammation, endoplasmic reticulum (ER)-stress, and apoptosis in RAW 264.7 cells. The results showed that DMPO at 50 mM inhibited inducible nitric oxide synthase expression when added shortly after LPS treatment ( 3 h). Interestingly, DMPO upregulated anti-inflammatory heme oxygenase-1 (HO-1) expression and reversed LPS-induced decrease in HO-1 expression. LPS could induce cellular ER stress as indicated by CHOP induction; DMPO reduced LPS effect on CHOP expression. Unexpectedly, DMPO had a synergistic effect with LPS on increased caspase-3 activity. It is possible that DMPO may activate some potent survival signaling pathways in the meantime that outcompete the apoptosis mechanisms. Our data provide clues for further understanding of DMPO therapeutic potential.