Lithostathine, the Presumed Pancreatic Stone Inhibitor, Does Not Interact Specifically with Calcium Carbonate Crystals
| Autor: | Max De Reggi, Véronique Stoven, Louis Patard, Bouchra Gharib |
|---|---|
| Přispěvatelé: | Centre de Bioinformatique (CBIO), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL) |
| Rok vydání: | 1998 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Nerve Tissue Proteins Plasma protein binding Biochemistry Calculi Calcium Carbonate 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pancreatic Juice Lithostathine Chemical Precipitation Humans Bovine serum albumin Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology Calcium metabolism 0303 health sciences biology Chemistry Calcium-Binding Proteins Albumin Pancreatic Diseases Cell Biology Phosphate Peptide Fragments Calcium carbonate 030220 oncology & carcinogenesis Pancreatic juice biology.protein Calcium Oligopeptides Protein Binding |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 1998, 273 (9), pp.4967-4971. ⟨10.1074/jbc.273.9.4967⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.273.9.4967 |
| Popis: | Lithostathine (pancreatic stone protein, Reg protein) is, in addition to albumin, the major nonenzymatic protein of the pancreatic juice. It has been assumed to inhibit calcium carbonate precipitation and therefore to prevent stone formation in the pancreatic ducts. This function is, however, debatable. The assumption is based on the inhibition of in vitro crystal nucleation and growth by lithostathine. Considering that these phenomena occur only under certain critical conditions, we re-examined the question using a protein preparation where the purity and folding have been tested by mass spectroscopy and NMR in the absence of nonprotein contaminants. Under these conditions, we showed conclusively that lithostathine does not inhibit calcium carbonate nucleation and crystal growth. We demonstrated that previous findings on the alleged inhibition can be attributed to the uncontrolled presence of salts in the protein preparation used. Moreover, the affinity of lithostathine to calcite crystals, expressed as the half-life of bound iodinated protein in the presence of unlabeled competitor, was significantly lower than that of bovine serum albumin (8.8 and 11.2 h, respectively). Using glass microspheres instead of crystals did not significantly change the half-life of bound lithostathine (8.0 h). These findings are incompatible with the hypothesis of a specific interaction of lithostathine with calcium carbonate crystals. In conclusion, considering that components of pancreatic juice such as NaCl and phosphate ions are powerful inhibitors of calcium carbonate crystal growth, the mechanism of stone formation in pancreatic ducts must be reconsidered. The presence in normal pancreatic juice of small amounts of the 133-residue isoform of lithostathine (PSP-S1), which precipitates at physiological pH, should be noted, and the possibility should be considered that they form micro-precipitates that aggregate and are progressively calcified. |
| Databáze: | OpenAIRE |
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