Proteases, lysosomal

Proudfoot AE, Buser R, Borlat F et al (1999) Amino-terminally modified RANTES analogues demonstrate differential effects on RANTES receptors. J Biol Chem 274 32478-32485 Qin AP, Zhang HE, Qin ZH (2008) Mechanisms of lysosomal proteases participating in cerebral ischemia-induced neuronal death. Neurosci Bull 24 117-123 Richter R, Bistrian R, Escher S et al (2005) Quantum proteolytic activation of chemokine CCL15 by neutrophil granulocytes modulates mononuclear cell adhesiveness. J Immunol 175 1599-1608... 

Necrosis is a dramatic and very rapid form of cell death in which essentially every compartment of the cell disintegrates. Necrosis is characterized by marked dysregulation of ion homeostasis resulting in cell swelling, dilation of mitochondria and the ER and the formation of vacuoles in the cytoplasm [33], Proteases play important roles in the degradation of cells during necrosis. In contrast to apoptosis, where caspases are the key death proteases, calpains and lysosomal proteases (cathepsins B and D, in particular) are major players in necrosis. Caspases may be activated in response to mitochondrial damage and... 

Kagedal, K., Bironaite, D., and Olhnger, K., 1999, Anthraquinone cytotoxicity and apoptosis in primary cultures of hepatocytes. Free Rad. Res. 31 419-428 Kagedal, K., Johansson, U., and Olhnger, K., 2001, The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress. FASEB J. (May 18, 2001) 10.1096/. 00-0708fje... 

Stoka, V., Turk, B., Schendd, S.L., Kim, T.-H., Cirman, T, Srripas, SJ., EUerby, L.M., Bredesen, L., Freeze, H, Abrahamson, M., Bromme, D., Krajewski, S., Reed, J.C., Yin, X.-M., Turk, V., and Salvesen G.S., 2001, Lysosomal Protease Pathways to Apoptosis. Cleavage of Bid, not pro-caspases, is the most likely route. J. Biol. Chem. 276 3149-3157 Srm, X. and Ross, D., 1996, Quinone-induced apoptosis in human colon adenocarcinoma ceUs via DT-diaphorase mediated bioactivation. Chem. Biol. Interact. 100 267-76 Taatjes, D.J. and Koch, T.H., 2001, Nuclear targeting and retention of anthracycUne antitumor dmgs in sensitive and resistant tumor ceUs. Curr. Med Chem. 8 15-29 Tarr, M. and van Helden, PT)., 1990, Inhibition of transcription by adriamycin is a... 

As discussed in detail by Dillard et al. and by Mittman et al. the possible relationship of lysosomal proteases to chronic lung disease has been inferred from the finding of an increased incidence of emphysema in subjects deficient in serum ai>antitrypsin factor, an -globulin that can inhibit lysosomal proteases. (No effect of ozone on serum aj-antitrypsin inhibitor was noted in rabbits chronically exposed to ozone. ) Thus, an ozone-induced increase in concentrations of such enzymes in the lung might produce excess proteolysis and result in eventual chronic lung disease. However, the available evidence is inadequate to support the belief that such a process occurs in humans intermittently exposed to ozone. Further studies of this potential hazard would be of value. 

Most of the lysosomal proteases called cathepsins are small 20- to 40-kDa glycoproteins found in all animal tissues.313 Most are cysteine proteases which function best and are most stable in the low pH reducing environment of lysosomes. They resemble papain in size, amino acid sequence, and active site structures. Papain is nonspecific but most cathepsins have definite substrate preferences. Cathepsin B is the most abundant. There are smaller amounts of related cathepsins H (an aminopeptidase)314 and L315 and still less of cathepsins C, K, and others. Cathepsin B is both an endopep-tidase and an exopeptidase.316 It acts on peptides with arginine at either Pj or P2 but also accepts bulky hydro-phobic residues in Pj and prefers tyrosine at P3.317 Cathepsin S is less stable at higher pH than other cathepsins and has a more limited tissue distribution, being especially active in the immune system.318 319... 

Lysosomal proteases are called cathepsins, a name derived from the Greek term meaning to digest. The interior of the lysosome is acidic and the cathepsins, like all lysosomal hydrolases, possess acidic pH optima and exhibit little enzymatic activity at neutral pH. This characteristic protects the cell from autolytic breakdown that might result from leakage of lysosomal contents into the neutral cytoplasm. 

Effector caspases are activated by a transactivation mechanism, which is characterized by the catalytic action of a mature caspase on a procaspase (Thornberry et al., 1997 Earnshaw et al., 1999 Slee et al., 1999). Nevertheless, their activation can also occur by the action of other proteases. Granzyme B, a serine-protease, also has proteolytic specificity for aspartic acid residues. It is able to cleave and directly activate caspase 3 (Darmon et al., 1995). Cathepsin B, a lysosomal protease, cleaves and activates procaspase 11 (Schotte et al., 1998). 

LDL binds specifically to lipoprotein receptors on the cell surface. The resulting complexes become clustered in regions of the plasma membrane called coated pits. Endocytosis follows (see Fig. 13-3). The clathrin coat dissociates from the endocytic vesicles, which may recycle the receptors to the plasma membrane or fuse with lysosomes. The lysosomal proteases and lipases then catalyze the hydrolysis of the LDL-receptor complexes the protein is degraded completely to amino acids, and cholesteryl esters are hydrolyzed to free cholesterol and fatty acid. New LDL receptors are synthesized on the endoplasmic reticulum (ER) membrane and are subsequently reintroduced into the plasma membrane. The cholesterol is incorporated in small amounts into the endoplasmic reticulum membrane or may be stored after esterification as cholesteryl ester in the cytosol this occurs if the supply of cholesterol exceeds its utilization in membranes. Normally, only very small amounts of cholesteryl ester reside inside cells, and the majority of the free cholesterol is in the plasma membrane. 

Secreted proteases and glycosidases may also contribute to a modification of the antibody structure this effect generally happens extracellularly. Karl et al.19 described an acidic protease in cell-free culture supernatant of a hy-bridoma culture with a similar activity of a lysosomal protease. This enzymatic activity could be inhibited by pepstatin A. Investigations of cell-free... 

G3. Gradehandt, G., and Ruede, E., The endo/lysosomal protease cathepsin B is able to process conalbumin fragments for presentation to T cells. Immunology 74(3), 393—398 (1991). 

Within the ileal mucosal cell, the vitamin is released by lysosomal proteolysis of intrinsic factor, and is bound to transcobalamin II, a vitamin B12 binding protein synthesized in the enterocytes. Transcobalamin II is in vesicles destined for export from the enterocytes, and it is assumed that vitamin B12 binds to the apoprotein in these vesicles rather than in the lysosomes, because otherwise newly synthesized transcobalamin would be hydrolyzed by lysosomal proteases (Seetharam, 1999). 

Clan CA is composed of twenty families. Family Cl within clan CA is divided into two subfamilies that consist of CIA (papain subfamily) and CIB (bleomycin hydrolase subfamily) groups. The larger subfamily CIA consists of secreted and lysosomal proteases that include the animal cysteine cathepsin proteases cathepsins B, H, and L as well as the plant proteases papain, chymopapain, and actinidain. 

Tobin DJ, Foitzik K, Reinheckel T, Mecklenburg L, Botchkarev VA, et al. The lysosomal protease cathepsin L is an important regulator of keratinocyte and melanocyte differentiation during hair follicle morphogenesis and cycling. Am. J. Pathol. 2002 160 1807-1821. 

Thyroid stimulating hormone (TSH) stimulates pinocytosis of thyroglobulin, and lysosomal proteases cleave peptide bonds, releasing free T3 and T4 into the blood. 

The receptor, which is internalized along with the hormone, may either be degraded by lysosomal proteases, or it may be recycled to the cell membrane. 

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