Biomaterial Database

Inhibition of interleukin 1-stimulated cartilage proteoglycan degradation by a lipophilic inactivator of cysteine endopeptidases. 1992

D J Buttle, and J Saklatvala, and M Tamai, and A J Barrett

Department of Biochemistry, Strangeways Research Laboratory, Worts Causeway, Cambridge, U.K.

Inactivators of cysteine endopeptidases were tested as inhibitors of the cytokine-stimulated release of proteoglycan from cartilage. The test system consisted of bovine nasal septum cartilage maintained in organ culture, and the stimulus was provided by recombinant human interleukin 1 alpha. L-3-Carboxy-2,3-trans-epoxypropionyl-leucylamido-(4-guanidin o)butane (E64) and L-3-carboxy-2,3-trans-epoxypropionyl-leucylamido-(3-methyl)b utane (Ep475) showed no inhibition at concentrations up to 100 microM. In contrast, trans-epoxysuccinyl-leucylamido-(3-methyl)butane ethyl ester (Ep453), a 'prodrug' of Ep475, was an effective inhibitor. The LL-, LD- and DL-isomers gave significant inhibition at 10 microM, and the DD-isomer was inhibitory at 100 microM. None of the isomers had any detectable effect on protein synthesis or glycolysis, and their inhibitory effects were reversible. Iodoacetate inhibited proteoglycan release by a general toxic effect. Our results suggest that cysteine endopeptidase(s) play a part in cytokine-stimulated cartilage breakdown, but that effective inhibitors must pass through membranes.

UI	MeSH Term	Description	Entries
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D007461	Iodoacetates	Iodinated derivatives of acetic acid. Iodoacetates are commonly used as alkylating sulfhydryl reagents and enzyme inhibitors in biochemical research.	Iodoacetic Acids,Acids, Iodoacetic
D007930	Leucine	An essential branched-chain amino acid important for hemoglobin formation.	L-Leucine,Leucine, L-Isomer,L-Isomer Leucine,Leucine, L Isomer
D011509	Proteoglycans	Glycoproteins which have a very high polysaccharide content.	Proteoglycan,Proteoglycan Type H
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002356	Cartilage	A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.	Cartilages
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015853	Cysteine Proteinase Inhibitors	Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.	Acid Cysteine Proteinase Inhibitor,Cysteine Protease Inhibitor,Cysteine Protease Inhibitors,Cysteine Proteinase Antagonist,Cysteine Proteinase Antagonists,Cysteine Proteinase Inhibitor,Cysteine Proteinase Inhibitors, Endogenous,Cysteine Proteinase Inhibitors, Exogenous,alpha-Cysteine Protease Inhibitor,Acid Cysteine Proteinase Inhibitors,alpha-Cysteine Protease Inhibitors,Antagonist, Cysteine Proteinase,Antagonists, Cysteine Proteinase,Inhibitor, Cysteine Protease,Inhibitor, Cysteine Proteinase,Inhibitor, alpha-Cysteine Protease,Inhibitors, Cysteine Protease,Inhibitors, Cysteine Proteinase,Inhibitors, alpha-Cysteine Protease,Protease Inhibitor, Cysteine,Protease Inhibitor, alpha-Cysteine,Protease Inhibitors, Cysteine,Protease Inhibitors, alpha-Cysteine,Proteinase Antagonist, Cysteine,Proteinase Antagonists, Cysteine,Proteinase Inhibitor, Cysteine,Proteinase Inhibitors, Cysteine,alpha Cysteine Protease Inhibitor,alpha Cysteine Protease Inhibitors
D019807	Iodoacetic Acid	A derivative of ACETIC ACID that contains one IODINE atom attached to its methyl group.	Monosodium Iodoacetate,Monoiodoacetic Acid,Sodium Iodoacetate,Acid, Iodoacetic,Acid, Monoiodoacetic,Iodoacetate, Monosodium,Iodoacetate, Sodium