Human parathyroid hormone (1-34) transiently increases the excretion of lysosomal enzymes into urine and the size of renal lysosomes.
It has been reported that the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, transiently increases in human after treatment with human parathyroid hormone (hPTH)(1-34). We report here that hPTH(1-34) caused transient changes in the size and density of rat renal lysosomes following urinary excretion of NAG and other lysosomal enzymes tested. Percoll density gradient centrifugation revealed that hPTH(1-34) slightly but significantly increased the fraction of high density lysosomes (around 1.12 g/ml) 5-10 min after the treatment with hPTH(1-34), with a concomitant decrease in the fraction of intermediate density lysosomes (1.07-1.08 g/ml). On electron micrographs, some lysosomes in proximal tubules but not in distal tubules showed a change in morphology from circular to oval, and became enlarged and electron-dense 5-10 min after the treatment with hPTH(1-34). These responses to hPTH(1-34) were also reversible and transient. NAG excreted in urine after treatment with hPTH(1-34) had the molecular mass of a mature form in lysosomes and/or endosomes and was not a prepro-and/or pro-form of the enzyme. Thus, the changes in the density and size of renal lysosomes appear to be associated with the exocytosis of lysosomal enzymes by hPTH(1-34).
Iwata
T
T
Division of Enzyme Chemistry, Institute for Enzyme Research, Teikyo University School of Medicine, Itabashi-ku, Tokyo, 173-8605, Japan.
Sakai
K
K
Hori
M
M
Uchida
S
S
Towatari
T
T
Kido
H
H
D000118:Acetylglucosaminidase / Q000652:urine*; D000135:Acid Phosphatase / Q000652:urine*; D000818:Animals; D002403:Cathepsins / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000648:ultrastructure; D008247:Lysosomes / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D000135:Acid Phosphatase; D000118:Acetylglucosaminidase; D002403:Cathepsins