Effects of various protein-modifying agents and the aminonucleoside of puromycin on dithioerythritol-reducible disulfide in glomerular basement membrane.

Comparative study of dithioerythritol-reducible (DTE) disulfide bonds in glomerular basement membranes (GBM) isolated from normal rats and from similar groups of rats treated with the nephrosis-producing aminonucleoside of puromycin emphasize not only the importance of such linkages in the interaction and structural organization of the macromolecular GBM collagen-glycoprotein matrix but also suggest a modality by which GBM semi-permeability might be engendered. Although DTE-reducible disulfide is significantly reduced in GBM of rats as early as the fourth day after administration of a nephrosis-producing dose of the aminonucleoside it has not been possible to demonstrate an unequivocal in vitro or direct effect of the drug on DTE-reducible disulfide in normal GBM. Several-fold increases in DTE-reducible disulfide in GBM subjected to the denaturing action of guanidine-HCl or the proteolytic action of pronase indicates that most of the disulfide lies buried in the GBM. Location of disulfide crosslinks in the innermost regions or core of the GBM might be expected to not only stabilize the membrane but also to protect the GBM from a considerable array of disulfide cleaving (reductases) within the kidney cortex.