Disease relevance of CTSH

• We found a significant increase in cathepsin H expression in high-grade prostatic intraepithelial neoplasia and carcinoma of the prostate [1].
• In order to evaluate the role of cysteine peptidase cathepsin H (Cath H) in human lung cancer its protein levels were determined in 148 pairs of lung tumour tissue and adjacent non-tumourous lung parenchyma using the enzyme-linked immunosorbent assay technique [2].
• Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer [3].
• Cathepsin H was isolated from human placenta by autolysis, acetone fractionation, and chromatography on DEAE-cellulose, Sephadex G-75, hydroxyapatite and concanavalin A-Sepharose [4].
• Immunoreactivities for cathepsin H additionally were found in cell parts containing secretory granules of B-cells and insulinoma cells [5].

Psychiatry related information on CTSH

• We have therefore been unable to confirm a potential role for lysosomal cathepsins in the characteristic neurodegeneration associated with Alzheimer's disease; however the finding of significant increases in activity of dipeptidyl aminopeptidase II, cathepsin H and cathepsin D specifically in cases with Huntington's disease is of particular note [6].

High impact information on CTSH

• It inhibits two other cysteine proteases, cathepsin H and papain, but to much lesser extent [7].
• We have determined the subcellular distribution of this enzyme and three additional lysosomal hydrolases (cathepsin H, beta-hexosaminidase, and beta-glucuronidase) in normal murine liver and six metastatic variants of the B16 melanoma [8].
• Faint staining of cathepsin H was also seen at the sites of rimmed vacuoles [9].
• Amino acid sequence comparison revealed that oryzains alpha and beta are similar not only to each other (70% similarity) but also to actinidin and papain (about 50%), whereas oryzain gamma was rather similar to aleurain (85%) and cathepsin H (60%) [10].
• The three oryzains are similar to one another and also to other known cysteine proteinases such as papain and cathepsin H with respect to the sequences around the active site residues and the COOH-terminal Trp-rich region [10].

Biological context of CTSH

• METHODS: genetic linkage analysis was performed with DNA markers in the region of BHMT, COL1A2 and CTSH [11].
• Crystal structure of Stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases [12].
• The complete amino acid sequences of human kidney cathepsin H (EC 3.4.22.16) and human kidney cathepsin L (EC 3.4.22.15) were determined [13].
• Papain, and to a minor extent cathepsin H, hydrolyzed the propeptide of cathepsin S, leading to competition with the hydrolysis of the fluorogenic substrates in the respective assays [14].
• Human cathepsin H: deletion of the mini-chain switches substrate specificity from aminopeptidase to endopeptidase [15].

Anatomical context of CTSH

• The expression of AKR1B1 in the additional cell lines exhibited significant correlations with sensitivities to 8 of the 23 drugs examined, while that of CTSH displayed a significant negative correlation with only one (MS-247) of the 27 drugs examined [16].
• To estimate the prognostic value of cathepsins B, H, L, D and stefins A and B in head and neck carcinoma, their concentrations in cytosols of primary tumours and adjacent normal tissue were measured (cathepsins B, D stefins A, B in 45, cathepsin L in 24 and cathepsin H in 21 patients) [17].
• In addition, cathepsin H and cystatin B were colocalized in type 2 alveolar epithelial cells [18].
• In addition, reactive astrocytes were also immunolabeled with cathepsin B. Cathepsin H and cathepsin L were detected in the cytoplasm of a small number of shrunken and pigmented neurons [19].
• Cathepsin H immunoreactivities showed an other pattern: they were found regularly in the secretory granules of A- and B-cells and insulinoma cells, and in lysosomes of A-cells [5].

Associations of CTSH with chemical compounds

• Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression [3].
• Cathepsin L and cathepsin H were assayed in the presence of dithiothreitol and Na2EDTA (2 mM each) with Z-Phe-Arg-NHMec (pH 5.5) and Lys-NNa (pH 6.5) respectively [20].
• Both proteinases are inhibited by traditional inhibitors of cysteine proteinases and E-64, but leupeptin turned to be more effective inhibitor of cathepsin L (Ki = 2.4 nM) than of cathepsin H (Ki = 9.2 microM), the latter enzyme being sensitive to puromycin and benzethonium chloride as well.(ABSTRACT TRUNCATED AT 250 WORDS)[20]
• In comparison to normal sera, cathepsin H concentrations were elevated in all asthmatic patients, concentrations of both stefins were decreased in steroid-independent asthmatics, and stefin A concentrations were increased in steroid-dependent asthmatics before therapy [21].
• The enzyme is stable over the pH range 5-7.5, whereas it becomes inactive on heating to 50 degrees C. Cathepsin H of human placenta, like the enzyme from other sources, hydrolyses protein and naphthylamide substrates, showing within the latter group the strongest preference towards arginine-beta-naphthylamide (pH optimum 6.8) [4].

Physical interactions of CTSH

• A model of the tertiary structure of cathepsin H and its complex with stefin B was constructed [22].

Regulatory relationships of CTSH

• Thus hydrogen peroxide (0.3 mM) or 4-hydroxynonenal (1 nM) inactivated cathepsin B without inhibiting cathepsin H or lysosomal hydrolases such as alpha-L-fucosidase [23].
• Our analyses of cathepsin H activity levels and protein forms in human colorectal cancers compared to matched control mucosa support the concept that altered proteinase expression patterns may reflect both cancer stage and site [24].
• Cathepsin H of the peritumoral cells may either promote invasion of the tumor cells by degradation of the extracellular matrix or may reflect an elevated activity of the surrounding immunological cells [25].
• Cathepsin H also activated and decreased the Mr of kidney inactive renin [26].

Other interactions of CTSH

• The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex [12].
• The introduction of a charged residue into S2 (variant V10R) created a more specific inhibitor to distinguish cathepsin B from cathepsin H [27].
• Exclusion of the COL1A2 and CTSH genes was possible in the large family that was analysed separately [11].
• The enzymes, except cathepsin C, are endopeptidases (reviewed in Kirschke et al., 1995), although cathepsin B was found also to be a dipeptidyl carboxypeptidase (Aronson and Barrett, 1978) and cathepsin H also an aminopeptidase (Koga et al., 1992) [28].
• Such N-terminal truncation of cystatin C caused >300-fold lower inhibition of papain, cathepsin B, L and K, whereas the cathepsin H activity was compromised by a factor of ca. 10. Similarly, truncation of cystatin D caused alleviated inhibition of all endogenous target enzymes investigated [29].

Analytical, diagnostic and therapeutic context of CTSH

• The opposite was true for stefin A (p = 0.0002; p = 0.002) and stefin B (p = 0.009; p = 0.003), and in disease-free survival also for cathepsin H (p = 0.055) [17].
• Two forms of cathepsin H, the full-length form (CTSH) and a truncated form with a 12-amino acid deletion in its signal peptide region (CTSHDelta10-21), were identified by cDNA sequence analysis [1].
• The profile of cathepsin H activity in normal muscle xenografts was different than those of cathepsins B and B-plus-L [30].
• In the first week, the cathepsin H diminished sharply to about one-third of the biopsied muscle level and then, by 3 weeks after transplantation, it had increased slightly to about half the original level [30].
• Northern blot analysis indicated that cathepsin H is predominantly synthesized in kidney [31].

References