AJP - Cell Physiology, Vol 255, Issue 6 C712-C718, Copyright © 1988 by American Physiological Society
Uracil ribonucleotide metabolism in rat and human glomerular epithelial and mesangial cells
F. Dumler and P. Cortes
Department of Medicine, Henry Ford Hospital, Detroit, Michigan 48202.
Uridine diphosphosugars (UDP-sugars: UDP-N-acetylglucosamine, UDP-glucose,
and UDP-glucuronic acid) are essential coenzymes for the synthesis of
glomerular basement membrane and mesangial matrix (GBM-MM). This study has
characterized UDP-sugar metabolism in rat and human glomerular cells in
tissue culture. Culture of rat mesangial cells in medium containing
dialyzed fetal calf serum resulted in UTP loss (28 +/- 4 nmol.mg
DNA-1.h-1); the addition of 2 microM orotate to this medium resulted in net
UTP accretion (5.42 +/- 0.06 nmol.mg DNA-1.h-1). Rat mesangial cells
demonstrated 16- and 29- to 46-fold greater UTP and UDP-sugar pools,
respectively, than whole glomeruli. In human mesangial cells, 6-azauridine
(500 microM) decreased UDP-sugar pools by 48% (P less than 0.05), whereas
uridine (50 microM) produced a 2.5-fold increase. Human and rat mesangial
cells had greater (1.8- to 6.1-fold) UDP-sugar pools than epithelial cells
and 1.7-3.4 times greater labeled precursor incorporation into UDP-sugars.
In conclusion, glomerular cells utilize both exogenous orotate and uridine
for ribonucleotide synthesis, and the extracellular concentration of these
precursors markedly influence the formation and cellular content of
UDP-sugars. Prominent differences exist between separate glomerular cell
populations in their metabolism of UDP-sugars. This may represent diverse
activity of glycosylating reactions.
