TY - JOUR
T1 - Biosynthetic regulation of proteoglycans by aldohexoses and ATP
AU - Kanwar, Yashpal
AU - Yoshinaga, Yasuhiko
AU - Liu, Zhengzhi
AU - Wallner, Elisabeth
AU - Carone, Frank
PY - 1992
Y1 - 1992
N2 - Biosynthetic regulation of renal glomerular heparan sulfate-proteoglycans by various aldohexoses (mannose, glucose, and galactose) was investigated. Isolated kidneys were perfused for 5 hr with medium containing [35S]sulfate, to label sulfated proteoglycans, or [35S]methionine, to label total glomerular proteins. All the hexoses, above 10 mM concentration, caused a significant decrease in the de novo synthesis of [35S]sulfate-labeled proteoglycans. The relative effectiveness of the hexoses was as follows: mannose ≫ glucose > galactose. The proteoglycans were of relatively lower molecular weights and exhibited reduced charge-density characteristics. Autoradiographic studies revealed a 2- to 3-fold decrease of grain density over the glomerular basement membrane and mesangial compartments, and immunoprecipitable heparan sulfate-proteoglycans were similarly decreased 2- to 3-fold. There was no significant decrease in the total [35S]methionine-labeled glomerular proteins or immunoprecipitable type IV collagen and laminin. Cellular ATP levels were dramatically reduced in all groups, and the maximal depletion was caused by mannose. Addition of ATP (0.1-1.0 mM) to the perfusion medium resulted in the normalization of the de novo synthesis and of the biochemical characteristics of heparan sulfate-proteoglycans. The relevance of decreased de novo synthesis of proteoglycans due to the depletion of ATP in hyperglycemic states is discussed in terms of increased glomerular permeability to plasma proteins, as seen in diabetes mellitus.
AB - Biosynthetic regulation of renal glomerular heparan sulfate-proteoglycans by various aldohexoses (mannose, glucose, and galactose) was investigated. Isolated kidneys were perfused for 5 hr with medium containing [35S]sulfate, to label sulfated proteoglycans, or [35S]methionine, to label total glomerular proteins. All the hexoses, above 10 mM concentration, caused a significant decrease in the de novo synthesis of [35S]sulfate-labeled proteoglycans. The relative effectiveness of the hexoses was as follows: mannose ≫ glucose > galactose. The proteoglycans were of relatively lower molecular weights and exhibited reduced charge-density characteristics. Autoradiographic studies revealed a 2- to 3-fold decrease of grain density over the glomerular basement membrane and mesangial compartments, and immunoprecipitable heparan sulfate-proteoglycans were similarly decreased 2- to 3-fold. There was no significant decrease in the total [35S]methionine-labeled glomerular proteins or immunoprecipitable type IV collagen and laminin. Cellular ATP levels were dramatically reduced in all groups, and the maximal depletion was caused by mannose. Addition of ATP (0.1-1.0 mM) to the perfusion medium resulted in the normalization of the de novo synthesis and of the biochemical characteristics of heparan sulfate-proteoglycans. The relevance of decreased de novo synthesis of proteoglycans due to the depletion of ATP in hyperglycemic states is discussed in terms of increased glomerular permeability to plasma proteins, as seen in diabetes mellitus.
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U2 - 10.1073/pnas.89.18.8621
DO - 10.1073/pnas.89.18.8621
M3 - Article
C2 - 1528871
AN - SCOPUS:0026726765
SN - 0027-8424
VL - 89
SP - 8621
EP - 8625
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 18
ER -