Human renin biosynthesis and secretion in normal and ischemic kidneys.
Published
Journal Article
The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradiosequencing showed that this molecule was generated by cleavage between Gly-23 and Leu-24, yielding a 43-amino acid proregion. Analysis of prorenin secreted by the kidney tissue yielded an identical sequence, indicating that prorenin is secreted without any further proteolysis. An examination of the kinetics of processing and secretion suggested that a majority of the newly synthesized prorenin is quickly secreted, while only a small fraction is processed intracellularly to the mature renin. The differences in secretion kinetics between prorenin and mature renin and the selective inhibition of prorenin secretion by monensin suggest that they are secreted independently via two pathways: a constitutive pathway probably from the Golgi or protogranules that rapidly release prorenin and a regulated pathway that secretes mature renin from the mature granules. A comparison of the kinetics of processing between normal and ischemic tissues suggests that renal ischemia leads to an overall increase in the rate of processing of prorenin to mature renin. In addition, prolonged biosynthetic labeling of renin in the ischemic kidney yielded two smaller molecular weight immunoreactive forms suggestive of renin fragments that may be degradative products. These fragments were not detected in normal kidney tissue labeled for similar lengths of time.
Full Text
Duke Authors
Cited Authors
- Pratt, RE; Carleton, JE; Richie, JP; Heusser, C; Dzau, VJ
Published Date
- November 1987
Published In
Volume / Issue
- 84 / 22
Start / End Page
- 7837 - 7840
PubMed ID
- 3317396
Pubmed Central ID
- 3317396
International Standard Serial Number (ISSN)
- 0027-8424
Digital Object Identifier (DOI)
- 10.1073/pnas.84.22.7837
Language
- eng
Conference Location
- United States