Increased expression of the multidrug resistance-associated protein 1 (MRP1) in kidney glomeruli of streptozotocin-induced diabetic rats.

Oxidative stress has been linked to the podocytopathy, mesangial expansion and progression of diabetic nephropathy. The major cell defence mechanism against oxidative stress is reduced glutathione (GSH). Some ABC transporters have been shown to extrude GSH, oxidised glutathione or their conjugates out of the cell, thus implying a role for these transporters in GSH homeostasis. We found a remarkable expression of mRNA for multidrug resistance-associated proteins (MRP/ABCC) 1, 3, 4 and 5 in rat glomeruli. Three weeks after induction of diabetes in glomeruli of streptozotocin-treated rats, we observed a decline in reduced GSH levels and an increase in the expression and activity of MRP1 (ABCC1). These lower GSH levels were improved by ex vivo treatment with pharmacological inhibitors of MRP1 activity (MK571). We conclude that increased activity of MRP1 in diabetic glomeruli is correlated with an inadequate adaptive response to oxidative stress.