LIVER REGENERATION (LR) AFTER PARTIAL HEPATECTOMY (PH) IS IMPAIRED IN KIR 6.2 KNOCKOUT (KIR6.2-/-) MICE

HEIT-BARBINI, FJ; VERA, MC; LORENZETTI, F; COMANZO, CG; LUCCI, A; CEBALLOS, MP; QUIROGA, AD; ALVAREZ, ML

Congreso; Sociedad Argentina de Investigaciones Clinicas; 2018

ATP sensitive potassium (K-ATP) channels are composed ofpore-forming Kir6.x (6.1 or 6.2) subunits and SUR1 or SUR2 regulatorysubunits. Kir6.2/K-ATP channels are expressed in the liverand, besides coupling cell metabolism to cell membrane potential,they play critical roles in the cellular responses for tissue protectionunder stress. It was reported that activation of liver mitochondrialKir6.1 channels improves LR after PH by keeping a higherATP content. On the other hand, Kir6.2-/- mice showed aggravatedLPS-induced liver injury, indicating the involvement of Kir6.2 in thepathology of liver disease. The aim of the present study was to evaluatethe role of Kir6.2 in LR after PH. Male C57/B6 wild type (WT)and Kir6.2-/- mice (n=4) were subjected to 2/3 PH. Forty-eight hourspost-PH, mice were euthanized and serum and liver samples wereobtained. Serum markers of liver function (alanine and aspartateaminotransferases and alkaline phosphatase) did not present differencesbetween WT and Kir6.2-/-. Liver to body weight ratio showeda tendency to be reduced in Kir6.2-/- mice (WT: 0.0306±0.0001;Kir6.2-/-: 0.0234±0.007). Western blot studies of Proliferating CellNuclear Antigen (PCNA) and Cyclin D1, markers of cell proliferation,showed significant differences between WT and Kir6.2-/-, with adiminution of the expression of both proteins in Kir6.2-/- mice (PCNA(arbitrary units): WT: 328±43, Kir6.2-/-: 77±20*; Cyclin D1 (arbitraryunits): WT: 149±11, Kir6.2-/-: 95±6*; *p