Multivariate analysis of the oscillation of intrarenal enzyme networks induced by aminopeptidase inhibitor

Abstract

Hemeostatic movements of the enzymatic system in the kidney were analyzed in mice given an aminopeptidase inhibitor, bestatin. In spite of the specific inhibition spectrum of this agent, changes occurred which involved unexpectedly extensive networks of enzymes including exopeptidases, endopeptidases, glycosidases, phosphatase and esterase. By means of multivariate analysis, several principal components were extracted from the movements of the enzyme networks. Time series analysis was performed especially on the first three principal components, since they accounted for almost 80% of the sample variation. Autocorrelation curves of the scores for these three components demonstrated sine curve type oscillations in bestatin treated mice in contrast to atypical ones in control animals. Thus, the seemingly bizarre movements of individual enzymes turned out to be the result of homestatic regulations of enzyme networks in the kidney. This kind of study seems essential for interpreting the chronic movements of enzyme levels in the blood or kidney tissues occurring after administration of physiologically active substances including enzyme inhibitors.