J Korean Med Sci.
2002 Feb;17(1):41-48. 10.3346/jkms.2002.17.1.41.
FKBP-12 Exhibits an Inhibitory Activity on Calcium Oxalate Crystal Growth in Vitro
- Affiliations
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- 1Institute for Medical Science and Department of Immunology, School of Medicine, Keimyung University, Taegu, Korea.
- 2Department of Microbiology, School of Medicine, Keimyung University, Taegu, Korea.
- 3Nephrology, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL60637, USA.
- 4Institute for Medical Science, Kosin University College of Medicine, Pusan, Korea. bkchoe@ns.kosinmed.or.kr
- 5Department of Internal Medicine, School of Medicine, Youngnam University, Taegu, Korea.
- KMID: 2157592
- DOI: http://doi.org/10.3346/jkms.2002.17.1.41
Abstract
- Urolithiasis and calcium oxalate crystal deposition diseases are still significant medical problems. In the course of nephrocalcin cDNA cloning, we have identified FKBP-12 as an inhibitory molecule of calcium oxalate crystal growth. lambdagt 11 cDNA libraries were constructed from renal carcinoma tissues and screened for nephrocalcin cDNA clones using anti-nephrocalcin antibody as a probe. Clones expressing recombinant proteins, which appeared to be antigenically cross-reactive to nephrocalcin, were isolated and their DNA sequences and inhibitory activities on the calcium oxalate crystal growth were determined. One of the clone lambdagt 11 #31-1 had a partial fragment (80 bp) of FKBP-12 cDNA as an insert. Therefore, a full-length FKBP-12 cDNA was PCR-cloned from the lambdagt 11 renal carcinoma cDNA library and was subcloned into an expression vector. The resultant recombinant FKBP-12 exhibited an inhibitory activity on the calcium oxalate crystal growth (Kd=10(-7) M). Physiological effect of the extracellular FKBP-12 was investigated in terms of macrophage activation and proinflammatory cytokine gene induction. Extracellular FKBP-12 failed to activate macrophages even at high concentrations. FKBP-12 seems an anti-stone molecule for the oxalate crystal deposition disease and recurrent stone diseases.
Keyword
MeSH Terms
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Animals
Base Sequence
Calcium Oxalate/*antagonists & inhibitors
Carcinoma, Renal Cell
Crystallization
DNA, Complementary
Extracellular Space
Glycoproteins/genetics
Humans
Kidney Calculi/*prevention & control
Kidney Neoplasms
Male
Mice
Mice, Inbred ICR
Molecular Sequence Data
Recombinant Fusion Proteins/genetics/metabolism
Tacrolimus Binding Protein 1A/genetics/*metabolism
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