Glycoprotein reutilization in regenerating microvilli after renal ischemia in rats.

Renal ischemia causes a reversible loss of microvillar membrane (MVM) of the proximal tubule cell and of MVM enzyme specific activities (S.A.). We sought to determine if recovery of the MVM glycoprotein was accomplished through de novo synthesis or recycling. Renal ischemia (25 min) was induced in rats by occlusion of the left renal artery, followed by 15 min or 4 hrs of reflow of blood. Radiolabelled fucose was injected into rats before or after ischemia and was used as a marker for new glycoprotein synthesis or recycling of prelabelled glycoprotein. Ischemia, followed by 15 min of reflow, caused a 49% reduction in protein associated with the isolated MVM fraction of the ischemic kidney. There was also a decrease in newly fucosylated glycoprotein in both homogenate and MVM fraction measured as S.A. or total amount of labeled glycoprotein. Pre-labelled glycoproteins had no change in S.A. in homogenates or MVM fractions of ischemic or contralateral kidneys. However, the total amount of labeled glycoprotein in the ischemic MVM fraction was reduced. At 4 hrs of reflow, protein content of the MVM fraction was back to normal. Pre-labelled glycoproteins of the ischemic homogenate and MVM fraction were also back to normal with no significant dilution of glycoprotein S.A. by newly synthesized protein, indicating that glycoprotein recycling occurs to a large extent in the ischemic kidney.

Regeneration of the renal brush border after renal ischemia in rats.

An early change following mild renal ischemia is the loss of the renal microvilli, which then regenerate morphologically within 6 h. We studied microvillar regeneration in rats with 25 min of renal artery occlusion and subsequent reflow. At subsequent intervals the rats were injected intraperitoneally with [14C]choline and [3H]leucine; 25 min later they were killed and their renal brush border membranes isolated. At 30 min of reflow of blood there was a 77% reduction in the incorporation of [3H]leucine into microvillar protein compared with that of the opposite control kidney (P less than 0.02). The incorporation rose to normal within 60 min. At 30 min of reflow, the incorporation of [14C]choline into phospholipids increased twofold (P less than 0.005), then returned toward normal values after 2 h. The altered incorporation of tracers was not due to change in membrane turnover or substrate pools. The activities of alkaline phosphatase, gamma-glutamyl transpeptidase, and alpha-glucosidase decreased 50% following ischemia (P less than 0.02) and returned to control values within 2 h. Thus, renal damage severe enough to partly efface microvilli is repaired metabolically within several hours.

Compensatory renal hypertrophy in the absence of androgen binding.

As a direct test for a role of androgens, compensatory renal hypertrophy was studied in normal male mice, in androgen-insensitive Tfm/Y mice, and in sibling normal female mice. Fifteen days after unilateral nephrectomy, although the kidneys of the normal male mice were larger, relative increases in renal weight were similar in all groups (33-43%). The magnitude of the increase and the contents of protein, RNA, and DNA were the same in the Tfm/Y mice and the female mice. Androgens are not essential to compensatory renal hypertrophy, but they promote larger mice with larger kidneys.