Abstract
Pancreatic stones of patients with chronic calcifying pancreatitis (CCP) are mostly made up of CaCO3 crystals. Formation and growth of such crystals is inhibited in vitro by lithostathine, a protein present in normal pancreatic juice. Decreased lithostathine activity was therefore suspected in patients with CCP, but comparison by immunoassay of lithostathine concentrations in the pancreatic juices of patients and controls led to conflicting results. This study shows that these discrepancies might have been caused in part by a remarkably high susceptibility of the protein to trypsin like cleavage, resulting in important structural changes and concomitant modifications of the epitopes. A novel lithostathine assay in juice was developed, based on separation of secretory proteins by high performance liquid chromatography. The chromatographic separation of lithostathine was based on hydrophobic interactions at pH 5.0 using a Phenyl-TSK column. This study showed with this assay that lithostathine concentrations (microgram/mg of total protein) were similar in CCP patients with alcoholic aetiology (mean (SD) 6.3 (2.7)) and other aetiologies (7.2 (3.7)), but one third of those estimated in patients without pancreatic disease (16.7 (4.3)). Similar concentrations were found, however, in chronic alcoholic patients without CCP (6.6 (3.3)) and in patients with CCP. It was concluded that decreased lithostathine concentration is associated with CCP, although such a decrease is not sufficient by itself for the disease to occur.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bernard J. P., Adrich Z., Montalto G., De Caro A., De Reggi M., Sarles H., Dagorn J. C. Inhibition of nucleation and crystal growth of calcium carbonate by human lithostathine. Gastroenterology. 1992 Oct;103(4):1277–1284. doi: 10.1016/0016-5085(92)91516-7. [DOI] [PubMed] [Google Scholar]
- Bernard J. P., Adrich Z., Montalto G., Multigner L., Dagorn J. C., Sarles H., De Caro A. Immunoreactive forms of pancreatic stone protein in six mammalian species. Pancreas. 1991 Mar;6(2):162–167. doi: 10.1097/00006676-199103000-00006. [DOI] [PubMed] [Google Scholar]
- Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
- De Caro A. M., Adrich Z., Fournet B., Capon C., Bonicel J. J., De Caro J. D., Rovery M. N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the 5th amino acid residue. Biochim Biophys Acta. 1989 Feb 23;994(3):281–284. doi: 10.1016/0167-4838(89)90305-1. [DOI] [PubMed] [Google Scholar]
- De Caro A. M., Bonicel J. J., Rouimi P., De Caro J. D., Sarles H., Rovery M. Complete amino acid sequence of an immunoreactive form of human pancreatic stone protein isolated from pancreatic juice. Eur J Biochem. 1987 Oct 1;168(1):201–207. doi: 10.1111/j.1432-1033.1987.tb13405.x. [DOI] [PubMed] [Google Scholar]
- De Caro A., Lohse J., Sarles H. Characterization of a protein isolated from pancreatic calculi of men suffering from chronic calcifying pancreatitis. Biochem Biophys Res Commun. 1979 Apr 27;87(4):1176–1182. doi: 10.1016/s0006-291x(79)80031-5. [DOI] [PubMed] [Google Scholar]
- De Caro A., Multigner L., Lafont H., Lombardo D., Sarles H. The molecular characteristics of a human pancreatic acidic phosphoprotein that inhibits calcium carbonate crystal growth. Biochem J. 1984 Sep 15;222(3):669–677. doi: 10.1042/bj2220669. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giorgi D., Bernard J. P., Rouquier S., Iovanna J., Sarles H., Dagorn J. C. Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and expression in chronic calcifying pancreatitis. J Clin Invest. 1989 Jul;84(1):100–106. doi: 10.1172/JCI114128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gross J., Brauer A. W., Bringhurst R. F., Corbett C., Margolies M. N. An unusual bovine pancreatic protein exhibiting pH-dependent globule-fibril transformation and unique amino acid sequence. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5627–5631. doi: 10.1073/pnas.82.17.5627. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gross J., Carlson R. I., Brauer A. W., Margolies M. N., Warshaw A. L., Wands J. R. Isolation, characterization, and distribution of an unusual pancreatic human secretory protein. J Clin Invest. 1985 Dec;76(6):2115–2126. doi: 10.1172/JCI112216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Montalto G., Lusher M., De Caro A., Multigner L., Sarles H., Delaage M. Analyse au moyen d'un anticorps monoclonal des composants du suc pancréatique humain apparentés à la protéine des calculs pancréatiques. C R Acad Sci III. 1985;300(6):199–202. [PubMed] [Google Scholar]
- Multigner L., Sarles H., Lombardo D., De Caro A. Pancreatic stone protein. II. Implication in stone formation during the course of chronic calcifying pancreatitis. Gastroenterology. 1985 Aug;89(2):387–391. doi: 10.1016/0016-5085(85)90341-5. [DOI] [PubMed] [Google Scholar]
- Nakagawa Y., Kaiser E. T., Coe F. L. Isolation and characterization of calcium oxalate crystal growth inhibitors from human urine. Biochem Biophys Res Commun. 1978 Oct 30;84(4):1038–1044. doi: 10.1016/0006-291x(78)91688-1. [DOI] [PubMed] [Google Scholar]
- Provansal-Cheylan M., Lusher M., De Caro A., Multigner L., Montalto G., Sarles H., Delaage M. Monoclonal antibodies to pancreatic stone protein. Radioimmunoassay and immunological comparison with trypsin 1. Biochimie. 1986 Sep;68(9):1109–1113. doi: 10.1016/s0300-9084(86)80185-7. [DOI] [PubMed] [Google Scholar]
- Provansal-Cheylan M., Mariani A., Bernard J. P., Sarles H., Dupuy P. Pancreatic stone protein: quantification in pancreatic juice by enzyme-linked immunosorbent assay and comparison with other methods. Pancreas. 1989;4(6):680–689. [PubMed] [Google Scholar]
- Sarles H., Camarena J., Gomez-Santana C. Radiolucent and calcified pancreatic lithiasis: two different diseases. Role of alcohol and heredity. Scand J Gastroenterol. 1992;27(1):71–76. doi: 10.3109/00365529209011170. [DOI] [PubMed] [Google Scholar]
- Sarles H., Dagorn J. C., Giorgi D., Bernard J. P. Renaming pancreatic stone protein as 'lithostathine'. Gastroenterology. 1990 Sep;99(3):900–901. doi: 10.1016/0016-5085(90)90999-h. [DOI] [PubMed] [Google Scholar]
- Sarles H. Definitions and classifications of pancreatitis. Pancreas. 1991 Jul;6(4):470–474. doi: 10.1097/00006676-199107000-00015. [DOI] [PubMed] [Google Scholar]
- Schlesinger D. H., Hay D. I. Complete covalent structure of statherin, a tyrosine-rich acidic peptide which inhibits calcium phosphate precipitation from human parotid saliva. J Biol Chem. 1977 Mar 10;252(5):1689–1695. [PubMed] [Google Scholar]
- Schmiegel W., Burchert M., Kalthoff H., Roeder C., Bützow G., Grimm H., Kremer B., Soehendra N., Schreiber H. W., Thiele H. G. Immunochemical characterization and quantitative distribution of pancreatic stone protein in sera and pancreatic secretions in pancreatic disorders. Gastroenterology. 1990 Nov;99(5):1421–1430. doi: 10.1016/0016-5085(90)91171-2. [DOI] [PubMed] [Google Scholar]