Disease relevance of Ctsl

• CONCLUSION: The constitutive expression of Ctsk and Ctsl messenger RNA in normal middle ear mucosa supports a function in the maintenance of middle ear mucosa homeostasis, and their downregulation as an early event in acute otitis media may reflect a disruption in that function [1].
• Cathepsin L and/or K participate in bone resorption based on bone type-1 collagen degradation and the L-type protease inhibitors suppressed the bone resorption [2].
• Gel mobility shift and competitive mobility shift assays indicated that this Inr element forms a DNA-protein complex with the HIV Inr-binding protein, LBP-1/CP2 or a homologue [3].
• Cathepsin L mRNA was also increased in tibialis anterior muscle of rats treated with the glucocorticoid analogue, dexamethasone, or rats bearing the Yoshida Sarcoma [4].
• At 1 week, foreign-body giant cells were observed around CP-1 and CP-2, but not around ARS or ZOE [5].

Psychiatry related information on Ctsl

• Thus, the results from this study demonstrate that beta-amyloid impacts on cathepsin-L as an upstream event in the neurodegenerative process and this result highlights the potential role of lysosomal components in the pathogenesis of Alzheimer's disease [6].

High impact information on Ctsl

• The 28- and 38-kD proteins were shown to be identical to the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the proenzyme form of cathepsin L, respectively [7].
• This intermediate compartment contained only small amounts of cathepsin L in comparison to lysosomes and was bound by a double membrane, typical of nascent vacuoles [8].
• Reduced cathepsin L activity, increased numbers of lysosomes, and the formation of meganeurites are all reported to occur during brain aging; thus, it is possible that the infusion of ZPAD into cultured slices sets in motion a greatly accelerated gerontological sequence [9].
• Hepatic collagenase activity was similar to the control; however, hepatic cathepsin B and cathepsin L activity and the intracellular degradation of newly synthesized collagen were markedly decreased 3, 5, and 7 days after partial hepatectomy compared with the controls [10].
• Furthermore the mature 29-kDa single-chain and 22-kDa heavy-chain forms of cathepsin L were undetectable in endosomes, although high levels of the 37-kDa proform were observed [11].

Chemical compound and disease context of Ctsl

• Although it is well known that cysteine proteases are strongly inhibited by kininogen, cathepsin L could represent an alternative pathway for kinin production in pathological processes [12].
• The mutagenic properties of 2-methylpropene (MP) and 2-methyl-1,2- epoxypropane (MEP) were investigated in the Salmonella assay [13].
• Four phthalate esters, namely, di(2-ethylhexyl) phthalate (DEHP, di-n-pentyl phthalate (DPP)., di-n-octyl phthalate (DOP), and diethyl phthalate (DEP) were investigated in vivo and their monoesters (MEHP, MPP, MOP, and MEP, respectively) in vitro for indications of Leydig cell toxicity in the rat [14].

Biological context of Ctsl

• RESULTS: Middle ear mucosa expression of a gene cluster encoding the lysosomal cysteine proteases, cathepsins B (Ctsb), L (Ctsl), and K (Ctsk), was modified after S pneumoniae challenge [1].
• The rate of hydrolysis of three cysteine-type proteinase substrates, N-benzyloxycarbonyl-Arg-Arg-4-methyl-7-coumarylamide (AMC) (cathepsin B), Arg-AMC (cathepsin H), and N-benzyloxycarbonyl-Phe-Arg-AMC (cathepsin L), were determined in rat lung throughout the time course of the induction of Pneumocystis carinii infection by immunosuppression [15].
• Analyses of a series of 5' deletion constructs demonstrated that a 120-base pair (bp) region that spans the transcription start site of the rat cathepsin L gene was sufficient to activate transcription in Sertoli cells isolated from sexually mature rats [16].
• A GC-box within the proximal promoter region of the rat cathepsin L gene activates transcription in Sertoli cells of sexually mature rats [16].
• Also cathepsin L participates in cell apoptosis mediated by caspase III activation [2].

Anatomical context of Ctsl

• Collectively, these results suggest that the GC-box is a critical regulatory element for the cathepsin L promoter in mature Sertoli cells [16].
• At stages VI-VII, CP-2/cathepsin L mRNA was present in Sertoli but not germ cells [17].
• In seminiferous tubules, CP-2/cathepsin L mRNA was undetectable at stage II, increased to maximal levels at stages VI and VIIa,b, and was again undetectable at stage XII [17].
• We propose that at stages V-VII, secreted CP-2/cathepsin L degrades adhesion molecules which bind compacted spermatids to Sertoli cells, thereby facilitating movement of these spermatids toward the lumen of the tubule [17].
• Previous studies demonstrated that secretion of Cyclic Protein-2 (CP-2) by mature rat Sertoli cells increased 30-fold from stage II to stages VI-VII of the cycle of the seminiferous epithelium and suggested that this protein was concentrated around compacted spermatids [17].

Associations of Ctsl with chemical compounds

• On gene array analysis, cathepsin L's message abundance was significantly increased by dexamethasone, and, by in vitro assay, cathepsin L created a 14-kDa carboxyl fragment that corresponded to the sole antigen detected in IEC-18 cell lysates as well as a 16.5-kDa fragment found in the media [18].
• Epoxy succinate peptide derivatives, CLIK-066, 088, 112, 121, 148, 181, 185 and 187, are typical specific inhibitors for cathepsin L. Aldehyde derivatives CLIK-060 and CLIK-164 showed specific inhibition against cathepsin S and cathepsin K, respectively [2].
• In addition, by using CM-cellulose column chromatography, cathepsin B and L were separated and the level of cathepsin L activity increased significantly [19].
• The sequence of rat liver cathepsin L determined at the protein level was identical with that deduced from the cDNA sequence except that in the heavy chain, residues 176-177 (Asp-Ser) were not present at the C-terminus and alanine was replaced by proline at residue 125 [20].
• The precursor showed a single protein band with Mr 39 kDa on SDS/polyacrylamide gel electrophoresis and was immunoreacted with the anti-rat cathepsin L antibody [21].

Regulatory relationships of Ctsl

• We found that Raf activation of the ERK mitogen-activated protein kinase pathway alone was sufficient to cause morphologic and growth transformation of the fibroblasts and was necessary and sufficient to alter cathepsin L expression and targeting [22].
• Furthermore, the expression of cathepsin L by germ cells isolated from 15-day-old rats (largely spermatocytes and spermatogonia) can be stimulated by Sertoli cell-enriched culture medium in a dose-dependent manner, but not by germ cell-conditioned medium [23].
• Interleukin-4 and -13 promote basolateral secretion of H(+) and cathepsin L by glomerular epithelial cells [24].

Other interactions of Ctsl

• Cathepsin B-like and cathepsin L-like activities fell below control values initially, but from week 8 of the immunosuppressive treatment significant increases above the control were noted [15].
• Although the component protein, P-cystatin alpha itself, inhibited cathepsin H strongly, these conjugated proteins inhibited specifically the cathepsin L family [25].
• In neither cell type did Ras expression increase the expression, processing or secretion of 2 other major lysosomal proteases, cathepsin B and cathepsin D. Thus, Ras utilizes different effectors to mediate transformation and to deregulate cathepsin L expression and secretion in fibroblast and epithelial cells [22].
• Studies on the substrate specificity indicated that the complex had tryptase-like activities towards various synthetic substrates, but no elastase, chymotrypsin, cathepsin-B and cathepsin-L activities [26].
• Furthermore, cathepsin L may play an important role in the degradation of the cartilaginous extracellular matrix in maturative and hypertrophic cell layers during successive developmental stages of the mandibular condyle [27].

Analytical, diagnostic and therapeutic context of Ctsl

• 1. Cathepsin L was purified from rat liver lysosomes by cell fractionation, osmotic disruption of the lysosomes in the lysosomal mitochondrial pellet, gel filtration of the lysosomal extract and chromatography on CM-Sephadex [28].
• By electron microscopy, nerve cells in DRG and SC contained lysosomes labeled by immunogold particles indicating cathepsins B and L, while immunogold particles for cathepsin L labeled lysosomes of glial cells [29].
• The isoelectric points of the multiple forms of cathepsin L extended from pH 5.8-6.1 ascertained by analytical isoelectric focusing [28].
• The concentrations of cathepsin L in various rat tissues and peripheral blood cells of rats were determined by a sensitive immunoassay, in which the minimum detectable amount of cathepsin L was 20 pg/assay [30].
• Enzymatic activity of cathepsin L increased 1.4-fold after 6 h of treatment with the high glucose, and then declined gradually to 72% of control cells after treatment for 36 h [31].

References