Low-density lipoprotein suppresses cathepsins B and L activity in rat mesangial cells

Disturbances of lipid metabolism are considered to play a pathogenetic role in glomerulosclerosis. Since intraglomerular have been proposed to be involved in the pathogenesis of the glomerulosclerosis, we have investigated the influence of LDL on the activity of the cellular proteases. Cathepsins B and L were measured with the aid of fluorometry, and 7-amido-4-methylocoumarin derivates were used as substrates; Z-Arg-Arg-AMC for cathepsin B, Z-Phe-Arg-AMC for cathepsins B and L together. Rat mesangial cells cultured 24 h in medium supplemented with LDL revealed inhibition of cathepsin B activity at concentrations of 250 micrograms LDL/ml medium, lower LDL concentrations were without apparent effect. Since the glomerular accumulation of structural and nonstructural proteins plays an important role in glomerulosclerosis, we conclude that the augmented proteolytic activity of mesangial cells might be one of the pathways located by which hyperlipidemia causes an increased susceptibility to glomerular damage.