The relationship between renin isoelectric forms and renin glycoforms

Abstract

Active renin can be separated into multiple isoelectric forms using shallow gradient isoelectric focusing and into multiple glycoforms using concanavalin A (Con A) affinity chromatography. The relationship between renin isoelectric forms and glycoforms has not been previously determined. In this study, each of three renin Con A glycoforms from rat kidney was composed of significantly different proportions of six renin isoelectric forms; glycoforms with the greatest affinity for Con A contained proportionally less of the acidic isoelectric forms than those with the least affinity for Con A. A set of compartmental models accurately predicted previously measured differential plasma clearance rates of the three renin glycoforms based on their corresponding isoelectric form proportions. We conclude that 1) each Con A renin glycoform is composed of significantly different proportions of isoelectric forms, and 2) the different proportions of isoelectric forms found in Con A glycoforms are sufficient to account for the differential renin plasma clearance rates demonstrated previously for renin glycoforms in the rat. These data suggest that the isoelectric and glycoform heterogeneity of active renin are, in fact, closely related and may result from variable and interrelated mannose (Con A affinity) and sialic acid (charge) attachments to renin.