ENDOCYTOSIS OF SERUM-ALBUMIN IN REGENERATING RAT-LIVER

Lysosomes, isolated from rat liver after 70% partial hepatectomy (PHX) , were found, by Western blotting, to contain a considerable amount of serum albumin. The level of intralysosomal serum albumin after PHX sh owed biphasic patterns: it increased immediately after PHX, peaked at 30 min, rapidly declined within a few hours, rose again with a peak at 15 hr, and gradually declined thereafter. At 15 hr after PHX, the con tent of lysosomal proteins in the liver increased to twice the level o f unoperated control, and the electron-microscopic observation of the isolated lysosomes revealed numerous large membrane-delimited structur es with ground substances of variable electron opacities, The increase in the intralysosomal serum albumin at 30 min and 15 hr was accompani ed by changes in the buoyant densities of endosomes in Percoll density gradients, At both time points, the density profiles of endosomes iso lated from hepatectomized rats shifted to the denser direction, sugges ting that PHX activates fusion and/or maturation of endosomes. Formald ehyde-treated bovine serum albumin is known to be taken up by the live r by receptor-mediated endocytosis. The uptake of the modified heterol ogous albumin was shown to be activated as early as 30 min after PHX, Both the uptake of serum albumin into lysosomes and the shift of buoya nt density profile of endosomes after PHX were inhibited by the admini stration of adrenergic receptor antagonists, particularly by the alpha (1)-antagonist prazosin, Further, the concentration of catecholamines in rat serum, particularly that of norepinephrine, was found to increa se immediately after PHX, relative to that in serum from sham-operated rats. These results suggest that the elevation of serum norepinephrin e levels after PHX activates endocytosis and facilitates delivery of e ndocytosed serum albumin to lysosomes, where albumin is digested to yi eld amino acids for possible use in protein synthesis during liver reg eneration.