Effect of acetaminophen on the membrane anchoring of Na+, K+ATPase of rat renal cortical cells

TRUMPER, L.; GABRIELA COUX; MONASTEROLO, L.; MOLINAS, S.; GARCIA, V. M. C.; ELIAS, M. M.

Biochimica et Biophysica Acta (Enzimology)

Elsevier

Año: 2005 vol. 1740 p. 332 - 339

0006-3002

In previous works we reported that the administration of a toxic dose of acetaminophen (APAP) induces acute renal failure (ARF) andpromotes changes on Na+, K+ATPase distribution in renal proximal plasma membranes. In the present work, we analyzed if APAP couldpromote the dissociation of Na+, K+ATPase from its membrane anchorage. The participation of calpain activation was also evaluated. Weanalyzed the Triton X-100 extractability of Na+, K+ATPase in freshly isolated cortical cell suspensions incubated with different APAPconcentrations (0.1, 1, 10 and 100 mM). Both a1 and h1 subunits were studied by Western blot. APAP promoted the increment of bothsubunits abundance in the Triton-soluble fraction. Calpain activation was detected in the membrane fractions of cells incubated with APAP.Incubation with APAP 0.1, 1 and 10 mM did not promote an increment in LDH release compared with controls, while APAP 100 mMpromoted an increased LDH release. Our results show that incubation of proximal cells with sublethal and lethal APAP concentrationspromotes the detachment of Na+, K+ATPase from its membrane anchoring. Inhibition of calpain activation by SJA 7029 protected againstAPAP-induced membrane damage but not against APAP-induced increase of the Triton X-100 extractability of Na+, K+ATPase.D 2004 Elsevier B.V. All rights reserved.