Disease relevance of Ctsh

• Molecular cloning of rat precursor cathepsin H and the expression of five lysosomal cathepsins in normal tissues and in a rat carcinosarcoma [1].
• Expression and the role of cathepsin H in human glioma progression and invasion [2].
• Cathepsin H antibody inhibited the invasion of glioblastoma cell lines through Matrigel invasion assay [2].
• Levels of cathepsin H antigen were found to be significantly higher in glioblastomas and anaplastic astrocytoma when compared with normal brain tissue and low-grade gliomas [2].
• 0. EPI of normal cells was heat stable, while that of psoriasis was reduced in activity after heating at 90 degrees C. Inhibitor activity of EPI from psoriatic cells toward the lysosomal enzymes, cathepsin B and/or cathepsin H and cathepsin L, was also inferior to EPI from normal cells at all pHs studied [3].

High impact information on Ctsh

• The 252-residue sequence of cathepsin B and the 220-residue sequence of cathepsin H were determined largely by automated Edman degradation of their intact polypeptide chains and of the two chains of each enzyme generated by limited proteolysis [4].
• A glycopeptide containing 3 amino acids, 2 glucosamines, and 6 mannoses was isolated from cathepsin H [5].
• It inhibits most thiol proteinases such as cathepsin H, L, B, and C, papain, and ficin, but not calcium-activated neutral proteinase or serine proteinases or carboxyl proteinases [6].
• Treatment of heavily infected animals with co-trimoxazole cleared the lungs of P. carinii, and this was accompanied by a marked reduction in proteinase activity, in particular, cathepsin H-like activity, which fell from 108- to 3-fold the mean control value following drug treatment [7].
• We also identified several genes involved with stress responses (cathepsin H, UBC2E, IGFBP3, smoothelin) [8].

Chemical compound and disease context of Ctsh

• Here we demonstrate significant similarities between the amino acid sequences of trypsin (a serine protease) and the N-terminal piece of a specific fragment of the poliovirus polyprotein encompassing the sequence of the viral proteinase 3C, and also between cathepsin H (a cysteine protease) and the C-terminal piece of the same fragment [9].

Biological context of Ctsh

• The amino acid sequence in the pro-peptide region, in particular, residues Phe-(-41) to Ser-(-29) of cathepsin H, is highly homologous to the pro-peptide regions of other cysteine proteinases [10].
• 1. A rat cathepsin H cDNA was isolated from a rat liver cDNA library with synthetic oligonucleotide probes [1].
• 5. The activity of cathepsin H does not change throughout this period nor do the cathepsins exhibit marked changes in activity in the placenta during this same period or in the PYS from days 12.5 to 14.5 of gestation [11].
• Under the optimal conditions the rate of leukotriene D4 transformation by cathepsin H was about 3% of the hydrolysis rate of alpha-N-benzoyl-DL-arginine-2-naphthylamide which is commonly utilized as a very efficient substrate to test the peptidase activity of the enzyme [12].
• This enzyme displayed a clear difference in substrate specificity when compared with other thiol proteases such as cathepsin B, cathepsin H, and cathepsin L, known to be present in the kidney [13].

Anatomical context of Ctsh

• The activities of cathespins B, L, and/or J were similar to those of liver or kidney lysosomes, but the levels of cathepsin H activity were much lower than those of liver or kidney lysosomes [14].
• Staining of cathepsin H was strong in panlobular hepatocytes, especially in the periphery of the cytoplasm, possibly representing the peribiliary dense bodies; and weaker in periportal sinusoidal cells, possibly Kupffer cells [15].
• Immunodeposits for cathepsin H only were demonstrated in lamellar bodies of Type II alveolar epithelial cells, suggesting the cosecretion of surfactants and cathepsin H from the cells into the alveolar space [16].
• Moreover, the presence of cathepsin H in secretory granules of the cells may indicate that the enzyme participates in the activation of secretory products [17].
• Moreover, immunoreactivity for cathepsin B appeared mainly in principal cells and was more intense in the head of the epididymis than in the tail, whereas that for cathepsin H appeared in both principal and clear cells and was more intense in the tail than the head [18].

Associations of Ctsh with chemical compounds

• Molecular cloning and sequencing of cDNA for rat cathepsin H. Homology in pro-peptide regions of cysteine proteinases [10].
• Cathepsin H isoenzymes hydrolyzed Arg-NNap and BANA, were totally inhibited by 1 mM p-CMB and only to 60% by 5.10(-5) M leupeptin [19].
• The specific substrates for cathepsin B (Z-Arg-Arg-NHMec) and cathepsin H (Arg-NHMec) were not hydrolysed by trypanopain-Tc under the conditions tested [20].
• The pH optimum for cathepsin B (substrate: Z-Arg-Arg-HNMec) and L (substrate: Z-Phe-Arg-HNMec in the presence of Z-Phe-Phe-CHN2) was approximately pH 6.0 for both glomeruli and renal cortex; while that for cathepsin H (substrate: Arg-HNMec) was approximately 6 [21].
• Transformation of leukotriene D4 catalyzed by lysosomal cathepsin H of rat liver [12].

Regulatory relationships of Ctsh

• Results have shown that cathepsin S has been expressed early than the cathepsin H in the nephrogenesis [22].

Other interactions of Ctsh

• Although the component protein, P-cystatin alpha itself, inhibited cathepsin H strongly, these conjugated proteins inhibited specifically the cathepsin L family [23].
• It was separated from cathepsin J using a Sephacryl S-200 gel-filtration column and was further separated from cathepsin H by DEAE-Sephadex A-50 anion-exchange column chromatography [24].
• Western blotting, however, revealed the presence of cathepsin H and cystatin beta in intermediate pituitary [17].
• These results showing that lysosomal aminopeptidases such as cathepsin H, cathepsin C and TPP-I are localized in lamellar bodies of type II alveolar epithelial cells strongly argue for the participation of lysosomal aminopeptidases in the formation process of surfactant containing specific proteins [25].
• Cathepsin B and dipeptidyl peptidase I were localized primarily in subsarcolemmal regions whereas cathepsin H and dipeptidyl peptidase II were scattered throughout the sarcoplasm consistent with other observation of two populations of muscle lysosomes [26].

Analytical, diagnostic and therapeutic context of Ctsh

• Analysis of cathepsin H isozyme patterns by fluorography following isoelectric focusing revealed differences between treated and control lung samples [7].
• Immunoblotting revealed that protein bands corresponding to the pro-form and mature form of cathepsin B and the mature form of cathepsin H were present in the culture medium [16].
• Determination of various cysteine proteinases by fluorometry revealed a significant decline of cathepsin B activity while the activities of cathepsin H and L were unchanged [27].
• By immunofluorescence staining, CH was found to be localized to the acrosome, middle piece, and principal piece [28].
• Variations in immunoreactivity for cathepsin H in rat type II alveolar epithelial (type II) cells and in its proteolytic activity in bronchoalveolar lavage fluid (BALF) were examined at six evenly spaced times over 24 hr (light period: 0600-1800 hr) [29].

References