Influence of protein nutrition on proteolytic activity and histone content in isolated mouse liver nuclei

The proteolytic activity in isolated liver nuclei from mice subjected to different conditions of protein nutrition and its relationship with histones metabolism was studied. After five days of protein depletion, the nuclear azocaseinolytic activity increases concomitantly with a decrease in the concentration of histones. This activity resembles, in localization, optimum pH and inhibition behavior to rat liver chromatin neutral proteinase that degrades histones. Moreover, these proteins were identified as its main endogenous substrates. Refeeding of the protein depleted mice for 16h with a normal diet was unable to either diminish proteolytic activity or recover the normal histone level. Activity of the multicatalytic proteinase complex (proteasome) was not detected in nuclei. Furthermore, treatments known to activate this enzyme were ineffective. Taken together, these results suggest that nuclear proteases are mainly involved in the regulation of histone levels.