Cathepsin activity

Lewis, T., Hartmann, C. B., and McCoy, K. L., Gallium Arsenide Modulates Proteolytic Cathepsin Activities and Antigen Processing by Macrophages, J. Immunol., 161, 2151, 1998. 

Nemova, N.N. and Sidorov, V.S. (1990). Dynamics of cathepsin activity in gonads of female fish during maturation (In Russian). Voprosy Ikhtiologii 30,516-519. 

Increased concentrations of muscle cathepsins have been recorded in many types of muscle atrophy. Acid cathepsin activity increases in dystrophic mouse muscle (W12) and in muscle from Duchenne-type dystrophy (P6) in the latter investigation, the elevation tended to be greater in the more advanced cases. Elevated acid cathepsin has been recorded also in denervation atrophy and vitamin E deficiency. Alkaline cathepsin activity has been shown to be higher in the dystrophic mouse (P7) and in Duchenne dystrophy (P12). 

It seems reasonable to suppose that the elevated cathepsin activity in dystrophic muscle, by enhancing muscle protein breakdown in vivo, is the cause of the increased rate of protein turnover the increased synthesis could then be seen as an adaptive response to the accelerated breakdown. There is yet, however, no real evidence that this is so the factors which control the breakdown of protein in muscle fibers are probably complex and little understood (PIO). A further possibility, that the proteins of atrophying muscles are in some way more susceptible to breakdown by proteolytic enzymes, seems unlikely Kohn (K9) reported that myosin from denervated rat muscle was digested normally by trypsin, and this was found to be true also of myosin from dystrophic mice and chickens (Kl), whereas Pollack and Bird (P21) stated that the autolytic activity of denervated muscle was not increased relative to the breakdown of hemoglobin by the muscle. 

P12. Pennington, R. J., and Robinson, J. E., Cathepsin activity in normal and dystrophic human muscle. Enzymol. Biol. Clin. 9, 175-182 (1968). 

An increased cathepsin activity having been found in infectious hepatitis in adults (65), we started both long-termed and ad hoc examinations of cases of infectious hepatitis and its sequelae (206). 

In the control group of 260 patients, in whom no hepatic nor biliary tract disease had been proved, 28 patients, that is, 10.8%, exhibited slightly positive cathepsin of this number 10 had peptic ulcer and 5 had chronic pancreatitis. Naturally it would be false to think that the cathepsin activity could be a specific test, because such a test is hardly... 

Figure 26. Polarographic determination of cathepsin in electrophoretic fractions after addition of inactivated serum. From left, four pairs of polarograms albumin, alpha, beta, and gamma globulins. Cathepsin activity found only in alpha and beta globulins.

Enzymological application of polarography was tried in the cerebrospinal fluid, the proteolytic activity being investigated after addition of inactivated serum as substrate (198). A comparison with the serum revealed the presence, in healthy subjects, of the cathepsin system in the cerebrospinal fluid, whereas in the serum two systems are found, viz., those of pepsinogen and cathepsin. The cathepsin activity in the cerebrospinal fluid is about half as high as that in the serum. In the cerebrospinal fluid of newborn infants lower values are found than in that of older children and adults. In 74 examinations no relationship with the diagnosis could be established, so that further study is necessary in this direction. 

For analysis of cathepsin, inactivated serum is needed as a supplementary substrate, as for the preceding determination of pepsinogen. Mix 6.5 ml of the buffer solution (reagent (xi), p. 531) for cathepsin activity determination with 0.2 ml of the analyzed serum and 0.4 ml of inactivated serum, stir, and pipette two 2-ml portions into separate test tubes. Put the first test tube—the proper test— into a thermostat at 37 C for 24 hours. Into the second tube—the control—add immediately 2 ml of 20% sulfosalicylic acid solution, drop by drop, shaking vigorously. Allow to stand for 10 min, and then filter in the way described before (p. 539, Brdi5ka filtrate reaction). The filtrate, which must be clear, may be stored at 4°C during the incubation of the proper test. After a 24-hr incubation, treat the test like the control (deproteinize by sulfosalicylic acid and filter, as described). 

Platt, M.O., et al. Cyclic pressure and shear stress regulate matrix metaUoproteinases and cathepsin activity in porcine aortic valves. J. Heart Valve Dis. 15(5), 622-629 (2006)... 

The unit of cathepsin activity was defined as the amount required to inactivate 1 nmol of enzyme substrate during a 30-minute incubation at 37°C, pH 5.0. The activities of the substrate enzymes were measured using standard procedures. For inactivation of Fru-P2ase the enzyme was assayed at pH 7.5. For activation of Fru-P ase by cathepsin B the enzyme was assayed at pH 9.2. The unit of activity is the amount required to increase the specific activity of Fru-Pjase by 1 unit/mg in a 30-minute incubation (S. Erickson-Viitanen et al, unpublished). 

Both muscular dystrophy (human and animal) and denervation atrophy are associated with increased concentrations of proteolytic enzymes in muscle. The likelihood that this is related to the enhanced protein turnover is clear, but evidence is scanty. Both acid [65, 82, 83] and alkaline [66, 83, 84] cathepsin activity increase in dystrophic muscle and either or both may be important in this respect. 

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