Cystatin-like Cysteine Proteinase Inhibitors from Human Liver

Overview

Journal Biochem J

Specialty Biochemistry

Date 1984 Mar 15

PMID 6426465

Citations 25

Authors

G D Green

A A Kembhavi

M E Davies

A J Barrett

Affiliations

Soon will be listed here.

Abstract

Cysteine proteinase inhibitor (CPI) forms from human liver were purified from the tissue homogenate by alkaline denaturation of cysteine proteinases with which they are complexed, acetone fractionation, affinity chromatography on S-carboxymethyl-papain-Sepharose and chromatofocusing. The multiple forms of CPI were shown immunologically to be forms of two proteins, referred to as CPI-A (comprising the forms of relatively acidic pI) and CPI-B (comprising the more basic forms). CPI-A and CPI-B are similar in their Mr of about 12400, considerable stability to pH2, pH11 and 80 degrees C, and tight-binding inhibition of papain, several related cysteine proteinases and dipeptidyl peptidase I. Ki values were determined for papain, human cathepsins B, H and L, and dipeptidyl peptidase I. The affinity of CPI-A for cathepsin B was about 10-fold greater than that of CPI-B, whereas CBI-B showed about 100-fold stronger inhibition of dipeptidyl peptidase I. For all the cysteine proteinases the liver inhibitors were somewhat less tight binding than cystatin. The resemblance of both CPI-A and CPI-B in several respects to egg-white cystatin is discussed. CPI-A seems to correspond to the epithelial inhibitor described previously, and CPI-B to the inhibitor from other cell types [Järvinen & Rinne (1982) Biochim. Biophys. Acta 708, 210-217].

Citing Articles

Progressive mitochondrial dysfunction in cerebellar synaptosomes of cystatin B-deficient mice.

Gorski K, Jackson C, Nyman T, Rezov V, Battersby B, Lehesjoki A Front Mol Neurosci. 2023; 16:1175851.

PMID: 37251643 PMC: 10213208. DOI: 10.3389/fnmol.2023.1175851.

The effects of Cstb duplication on APP/amyloid-β pathology and cathepsin B activity in a mouse model.

Wu Y, Whittaker H, Noy S, Cleverley K, Brault V, Herault Y PLoS One. 2021; 16(7):e0242236.

PMID: 34292972 PMC: 8297773. DOI: 10.1371/journal.pone.0242236.

A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L.

Dana D, Pathak S Molecules. 2020; 25(3).

PMID: 32041276 PMC: 7038230. DOI: 10.3390/molecules25030698.

Journey of cystatins from being mere thiol protease inhibitors to at heart of many pathological conditions.

Shamsi A, Bano B Int J Biol Macromol. 2017; 102:674-693.

PMID: 28445699 PMC: 7112400. DOI: 10.1016/j.ijbiomac.2017.04.071.

Characterization of PTZ-induced seizure susceptibility in a down syndrome mouse model that overexpresses CSTB.

Brault V, Martin B, Costet N, Bizot J, Herault Y PLoS One. 2011; 6(11):e27845.

PMID: 22140471 PMC: 3227573. DOI: 10.1371/journal.pone.0027845.

References

Barrett A . Cathepsin D. Purification of isoenzymes from human and chicken liver. Biochem J. 1970; 117(3):601-7. PMC: 1178965. DOI: 10.1042/bj1170601. View

Udaka K, Hayashi H . FURTHER PURIFICATION OF A PROTEASE INHIBITOR FROM RABBIT SKIN WITH HEALING INFLAMMATION. Biochim Biophys Acta. 1965; 97:251-61. DOI: 10.1016/0304-4165(65)90089-9. View

Barrett A . Chicken alpha2-proteinase inhibitor: a serum protein homologous with ovoinhibitor of egg white. Biochim Biophys Acta. 1974; 371(1):52-62. DOI: 10.1016/0005-2795(74)90154-8. View

Robinson G . Isolation and characterization of papaya peptidase A from commercial chymopapain. Biochemistry. 1975; 14(16):3695-700. DOI: 10.1021/bi00687a028. View

Roughley P, Murphy G, Barrett A . Proteinase inhibitors of bovine nasal cartilage. Biochem J. 1978; 169(3):721-4. PMC: 1183848. DOI: 10.1042/bj1690721. View

Jarvinen M . Purification and some characteristics of the human epidermal SH-protease inhibitor. J Invest Dermatol. 1978; 71(2):114-8. DOI: 10.1111/1523-1747.ep12546165. View

Jarvinen M, Rasanen O, Rinne A . The low-molecular-weight SH-protease inhibitor in rat skin is epidermal. J Invest Dermatol. 1978; 71(2):119-21. DOI: 10.1111/1523-1747.ep12546254. View

Baines B, Brocklehurst K . A necessary modification to the preparation of papain from any high-quality latex of Carica papaya and evidence for the structural integrity of the enzyme produced by traditional methods. Biochem J. 1979; 177(2):541-8. PMC: 1186404. DOI: 10.1042/bj1770541. View

LENNEY J, Tolan J, Sugai W, Lee A . Thermostable endogenous inhibitors of cathepsins B and H. Eur J Biochem. 1979; 101(1):153-61. DOI: 10.1111/j.1432-1033.1979.tb04227.x. View

10.

Hibino T, Fukuyama K, Epstein W . In vitro and in vivo inhibition of rat liver cathepsin L by epidermal proteinase inhibitor. Biochem Biophys Res Commun. 1980; 93(2):440-7. DOI: 10.1016/0006-291x(80)91097-9. View

11.

Hibino T, Fukuyama K, Epstein W . Chemical characterization, synthesis and distribution of proteinase inhibitor in newborn rat epidermis. Biochim Biophys Acta. 1980; 632(2):214-26. DOI: 10.1016/0304-4165(80)90079-3. View

12.

Saklatvala J, Barrett A . Identification of proteinases in rheumatoid synovium. Detection of leukocyte elastase cathepsin G and another serine proteinase. Biochim Biophys Acta. 1980; 615(1):167-77. DOI: 10.1016/0005-2744(80)90020-0. View

13.

Schwartz W, Barrett A . Human cathepsin H. Biochem J. 1980; 191(2):487-97. PMC: 1162239. DOI: 10.1042/bj1910487. View

14.

Kominami E, Wakamatsu N, Katunuma N . Endogenous thiol protease inhibitor from rat liver. Biochem Biophys Res Commun. 1981; 99(2):568-75. DOI: 10.1016/0006-291x(81)91783-6. View

15.

Rinne A, Jarvinen M, Rasanen O, Dorn A . [Demonstration of an epidermal SH-protease inhibitor in normal epithelium and in some human neoplasms--an immunological study (author's transl)]. Acta Histochem Suppl. 1980; 22:325-9. View

16.

Hirado M, Iwata D, Niinobe M, Fujii S . Purification and properties of thiol protease inhibitor from rat liver cytosol. Biochim Biophys Acta. 1981; 669(1):21-7. DOI: 10.1016/0005-2795(81)90218-x. View

17.

Kopitar M, Brzin J, Locnikar P, Turk V . Inhibitory mechanism of sericystatin, an intracellular proteinase inhibitor, reacting with cysteine proteinases. Hoppe Seylers Z Physiol Chem. 1981; 362(10):1411-4. View

18.

Coombs G . Proteinases of Leishmania mexicana and other flagellate protozoa. Parasitology. 1982; 84(1):149-55. DOI: 10.1017/s003118200005174x. View

19.

Brzin J, Kopitar M, Locnikar P, Turk V . An endogenous inhibitor of cysteine and serine proteinases from spleen. FEBS Lett. 1982; 138(2):193-7. DOI: 10.1016/0014-5793(82)80439-0. View

20.

Barrett A, KIRSCHKE H . Cathepsin B, Cathepsin H, and cathepsin L. Methods Enzymol. 1981; 80 Pt C:535-61. DOI: 10.1016/s0076-6879(81)80043-2. View