Disease relevance of CTSB

• The lysosomal protease cathepsin B has been implicated in a variety of pathologies including pancreatitis, tumor angiogenesis, and neuronal diseases [1].
• Cathepsin B (EC 3.4.22.1) was purified 746-fold with a 21% recovery from bovine brain by autolysis, fractional precipitation with acetone, carboxy-methyl-Sephadex chromatography, affinity chromatography on a cystamine containing column and gel filtration chromatography [2].
• The degradative effect of cathepsin B on MBP suggests a role for this proteinase in inflammatory demyelination [2].
• These data and the myocardial infarction size reducing action of NCO-700 might support the view that NCO-700 sensitive protease(s) - possibly, calcium-activated neutral protease and/or cathepsin B - is (are) working to induce an irreversible proteolysis in the process of myocardial cell degradation [3].

Psychiatry related information on CTSB

• Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer's disease [4].

High impact information on CTSB

• Cleavage is enhanced by the addition of exogenous bovine cathepsin B and inhibited in the presence of specific cysteine protease inhibitors, but not inhibitors of other proteases [5].
• The cDNA sequence encoding the precursor of cathepsin B of Schistosoma mansoni was cloned in a modified RNA expression vector pSP65 and the derived RNA expressed in rabbit reticulocyte lysates [5].
• CONCLUSION: Elevated coefficients of friction in arthritic joints occur concurrently with enhanced proteolytic degradation by up-regulated cathepsin B and other proteases, as well as decreased lubricin synthesis by synovial fibroblasts and superficial zone chondrocytes [6].
• Cathepsin B regulates the intrinsic angiogenic threshold of endothelial cells [1].
• Aclacinomycin A had no effect on cathepsin B, stimulated trypsin, and inhibited chymotrypsin and, to a lesser extent, calpain [7].

Biological context of CTSB

• In agreement with active-site titrations, there is no difference in cathepsin B mRNA levels between cultured myoblasts and myotubes, but lower levels of mRNA are found in fetal muscle [8].
• Amino acid sequence of bovine spleen cathepsin B [9].
• Bovine spleen cathepsin B shows 80% sequence homology with cathepsins B from other species [9].
• Substrate specificity of bovine cathepsin B and its inhibition by CA074, based on crystal structure refinement of the complex [10].
• Because micro-heterogeneities were previously reported in the cathepsin B primary structure, sequence polymorphism in the protein coding region was then investigated by PCR sequencing of genomic fragments and RNase protection assays [11].

Anatomical context of CTSB

• In fetal muscle, cathepsin B and L activities are 2-4-fold orders of magnitude lower than in cultured myoblasts [8].
• Kinetic studies revealed that the catalytic efficiency (kcat/Km) of cathepsin B is 2-3-fold higher in myotubes than in myoblasts [8].
• Purified cathepsin B from porcine parathyroid glands was allowed to act upon radioactive bovine parathormone and proparathormone at various ratios of enzyme to substrate and for different times [12].
• The subcutaneous route of administration of (acyloxy)methyl ketone 8 also provided potent cathepsin B inhibition in certain peripheral tissues (e.g., ED50 1.0 mg/kg for skeletal muscle, 0.1 mg/kg for heart) [13].
• Partial purification of cathepsin B in the bovine ciliary body and iris [14].

Associations of CTSB with chemical compounds

• An outstanding feature of bovine spleen cathepsin B not observed with the other cathepsins B is the presence of two additional half-cystine residues [9].
• Identification of the active site cysteine and of the disulfide bonds in the N-terminal part of the molecule of bovine spleen cathepsin B [15].
• However, at pH 7.0, the stability of cathepsin B decreased with increasing reduction potential and ambient cystine concentration [16].
• The intra- and interchain thiol-disulfide exchange reactions accompanying the denaturation of cathepsin B were investigated by polyacrylamide gel electrophoresis in SDS and by gel filtration experiments [17].
• The ability of cystamine, bis-N-aminoethyl disulfide, to inactivate cathepsin B by disulfide exchange is considerably enhanced by the addition of hydrophobic residues which apparently occupy secondary binding sites in the extended active center of the protease [18].

Other interactions of CTSB

• Activities of cathepsin B and L, but not cathepsin H, increase during bovine myogenic differentiation [8].
• However, some genes such as Cathepsin B (P = 0.0677), RAD50 (P = 0.0899), and TCP1 (P = 0.0824) tended to show higher expression in the early cleaving than in the late cleaving embryo [19].
• Cathepsin C, another cysteine proteinase with a rather different substrate specificity (i.e., aminopeptidase), was not inactivated by 8, indicating that the inactivation of papain and cathepsin B by azapeptide esters is a specific process [20].
• Cathepsin D appears to be mainly responsible for the initial cleavage of myoglobin, while cathepsin B catalyzes the C-terminal trimming of initially released fragments [21].
• Cathepsin D and cathepsin B are endosomal/lysosomal proteases that are thought to play a role during in vivo antigen processing, releasing fragments for binding to major histocompatibility complex class II products and subsequent presentation to T cells [22].

Analytical, diagnostic and therapeutic context of CTSB

• The different catalytic efficiency of cathepsin B in myotubes and myoblasts was related neither to modifications of mRNA size, as revealed by Northern blot analysis, nor to a different Mr of the active enzyme, as revealed by affinity labeling with benzyloxycarbonyl-Tyr(-125I)-Ala-CHN2, but to limited differences in cathepsin B isozymes [8].
• Inactivation of cathepsin B by active site-directed disulfide exchange. Application in covalent affinity chromatography [18].
• Immobilization of the peptidyl cystamine derivatives provided an effective and rapid procedure for the covalent chromatography of cathepsin B following ammonium sulfate fractionation of beef spleen or pork liver homogenates, replacing the need for ion exchange chromatography [18].
• Crystallization and preliminary X-ray study of the cathepsin B complexed with CA074, a selective inhibitor [23].
• Purified bovine cathepsin B treated briefly with 15 microM HNE lost approximately 76% of its protease activity and also developed immunoreactivity with antibodies to HNE adducts in Western blot analysis [24].

References