Shedding of Fas ectodomain that affects apoptosis of hepatocytes occurring in regenerative liver

On the basis of comprehending several membrane proteins undergoing ectodomain shedding, including tumor necrosis factor (TNF) alpha receptors, we want to know if Fas (CD95/APO-1), which belongs to the TNF receptor (TNFR) superfamily and transduces signals resulting in apoptosis upon binding of Fas ligand (L) or agonistic anti-Fas antibody, is shed on its ectodomain during liver regeneration After purification of the total membrane protein of hepatocytes, we analyzed Fas ectodomain shedding, using Western blotting, and determined the effect of Fas shedding on the apoptosis of hepatocytes by a statistical method relevant to apoptosis. Fas protein ectodomain shedding occurred at 2, 12, and 36 h after partial hepatectomy, and its level decreased at 2 months after partial hepatectomy. The same results were gained from in-vitro cultured hepatocytes induced by serum from rats after partial hepatectomy. The sensitivity of hepatocytes to agonistic anti-Fas antibody increased significantly after they were treated with serum from rats after partial hepatectomy. However, the expression of Fas mRNA and Fas protein did not affect the liver regeneration. Fas ectodomain shedding might be an important mechanism in controlling hepatocyte apoptosis during liver regeneration.