FKBP-12 Exhibits an Inhibitory Activity on Calcium Oxalate Crystal Growth in Vitro.
10.3346/jkms.2002.17.1.41
- Author:
In Sook HAN
1
;
Yasushi NAKAGAWA
;
Jong Wook PARK
;
Min Ho SUH
;
Sung IL SUH
;
Song Woo SHIN
;
Su Yul AHN
;
Byung Kil CHOE
Author Information
1. Institute for Medical Science and Department of Immunology, School of Medicine, Keimyung University, Taegu, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Tacrolimus Binding Protein 1A;
Calcium Oxalate;
Growth Inhibitor;
Nephrocalcin;
Anti-stone agent
- MeSH:
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
- From:Journal of Korean Medical Science
2002;17(1):41-48
- CountryRepublic of Korea
- Language:English
-
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.
