The compensatory growth of the kidney which is induced by unilateral nephrectomy is a highly regulated process resulting principally in hypertrophy of the remaining kidney. The events which regulate this process are unknown. We have examined the levels of transcripts for the proto-oncogenes, myc, H-ras, K-ras, and fos, and the cellular genes, H4 histone, ornithine aminotransferase, and gamma-glutamyl transpeptidase, following unilateral nephrectomy in the rat. The pattern of expression of c-myc, c-H-ras, and c-K-ras during compensatory growth of the kidney differs from the pattern of expression of these proto-oncogenes during liver regeneration, in which, unlike the kidney, hyperplasia rather than hypertrophy predominates. The lack of change in the abundance of these proto-oncogene transcripts following unilateral nephrectomy suggests a primary relationship between the expression of these proto-oncogenes and DNA synthesis and indicates there may be separate signals for cell growth, one to double cell size and one to replicate DNA. Increased mRNA transcripts for the enzymes ornithine aminotransferase and gamma-glutamyl transpeptidase were induced in the contralateral kidney after nephrectomy. The time course of expression for these two enzymes differs. The early expression of the gamma-glutamyl transpeptidase gene may indicate an involvement of this glutathione-metabolizing enzyme during renal compensatory growth, while the function of the delayed increase in ornithine aminotransferase transcripts in the remaining kidney is not apparent.

Proximal tubules from dog kidney were incubated for 2-6 min with low concentrations of pyruvate, glutamine, and malate. When initial medium citrate was between 0 and 0.5 mM and alpha-ketoglutarate was between 0 and 0.1 mM, concentrations of these two substrates in tubules and media after incubation were lower with 10 than with 40 mM HCO3-. Malate levels in tubules and media changed in the opposite direction. CO2 formation from labeled citrate or alpha-ketoglutarate was greater at low than at high HCO3-. In tubules treated with digitonin to disrupt the cell membrane, differences in citrate and alpha-ketoglutarate concentrations in tubules at high and low HCO3- were eliminated. The effects of acid-base changes seen in intact tubules on malate levels and on the rate of oxidation of labeled citrate persisted after digitonin pretreatment. These results show that acute effects of acid-base changes on citrate, alpha-ketoglutarate, and malate levels observed in intact renal cortex can be reproduced in isolated tubules. They suggest that these changes are related to changes in levels of citrate and alpha-ketoglutarate in cytoplasm without corresponding changes within mitochondria.