Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1389183 (autodigestion)
 317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new chemotactic factor for neutrophils is generated from calcium dependent cysteine proteinase (calpain) I by autodigestion. An active peptide was isolated from the autodigest and its structure was determined to be an acetylated nonapeptide with the sequence: N-acetyl Ser-Glu-Glu-Ile-Ile-Thr-Pro-Val-Tyr. Compared with the entire sequence of human calpain I, the peptide was identical with the N-terminal amino acid sequence of the large subunit deduced from the cDNA sequence, except that the peptide was devoid of a methionine residue and acetylated at the N-terminus. The acetyl nonapeptide was synthesized and its chemotactic activity was reconfirmed. The biological significance and possible role of this calpain derived chemotactic factor in inflammation are discussed.
 ...
PMID:Calcium dependent cysteine proteinase is a precursor of a chemotactic factor for neutrophils. 255 4

There are two types of calcium-activated neutral protease (CANP), m-CANP and mu-CANP, following the nomenclature of Suzuki et al to show that each requires mM and microM Ca2+, respectively, for its activation. We found mu-CANP activity in a crude CANP fraction extracted from the peripheral nerve, which degraded the neurofilament (Nf) triplet (200 K, 160 K, 68 K), especially the 160 K component, at Ca2+ concentrations of 50 microM and 0.1 mM. The triplet was degraded in the order of the 160 K, 68 K, and 200 K components, respectively. In addition, the effects of partially purified mu-CANP of rabbit skeletal muscle, purified natural mu-CANP of bovine liver, derived mu-CANP prepared by autodigestion of chicken muscle m-CANP, m-CANP of chicken skeletal muscle, and cathepsin B of rat liver on the Nf were examined. Among the triplet components, the 160 K component was most rapidly degraded by all proteases so far tested. The difference in the effect of mu-CANP and m-CANP or cathepsin B on susceptibility of the 200 K component to degradation might be due to the difference of the relative amounts of enzymes to Nf.
 ...
PMID:Calcium-activated neutral protease in the peripheral nerve, which requires microM order Ca2+, and its effect on the neurofilament triplet. 298 90

Mn2+ (50 microM) satisfies the requirement for activity of the purified Ca2+-dependent neutral proteinase from human erythrocytes. Unlike the activation by Ca2+ [E. Melloni et al. (1984) Biochem. Int. 8, 477-489], the effect of Mn2+ is fully reversible and does not involve autodigestion of the native 80-kDa catalytic subunit. However, the native dimeric proenzyme (procalpain), which contains both the 80-kDa subunit and a smaller 30-kDa subunit, is not activated by Mn2+ alone but also requires the presence of micromolar concentrations of Ca2+. Under these conditions, 40% of the maximum activity is expressed without dissociation of the 80- and 30-kDa subunits. Mn2+, but not micromolar Ca2+, can also partially satisfy the metal requirement of the native 80-kDa subunit isolated after dissociation of the heterodimer. This activity is further enhanced by the addition of 5 microM Ca2+, which is ineffective in the absence of Mn2+. After procalpain is converted to active calpain by incubation with Ca2+ and substrate [S. Pontremoli et al. (1984) Biochem. Biophys. Res. Commun. 123, 331-337] full activity is observed with 5 microM Mn2+, which now substitutes completely for Ca2+. Activation of procalpain by Mn2+ represents a new mechanism for modulation of the Ca2+-dependent proteinase activity.
 ...
PMID:The reversible activation by Mn2+ ions of the Ca2+-requiring neutral proteinase of human erythrocytes. 298 54

Some endogenous substrates were incubated with two forms of calcium-activated neutral protease (CANP) with high (muCANP) and low (mCANP) sensitivities to calcium ions. In addition to analyses of the processes of their degradation, changes in the molecular properties of these CANPs were also examined. Among the tested substrate proteins, the myosin heavy chain of rabbit skeletal muscle myofibrils and spectrin or band 3 protein of human erythrocyte membranes were degraded relatively rapidly. So far as these proteins were concerned, a higher degradation velocity was observed for muCANP than for mCANP. Vimentin from ascites tumor cells was degraded most rapidly and no difference was observed in degradation velocity between muCANP and mCANP. In all cases, muCANP and mCANP produced different proteolytic peptide fragments, suggesting the different substrate-specificities of these CANPs. The degradation of substrates always accompanied the autodigestion of CANPs, and the small subunits of both CANPs were degraded in the early stage of the autodigestion. The large subunit of muCANP (79K) was converted to a 76K polypeptide via a 77K polypeptide as an intermediate. The autodigested muCANP with 76K polypeptide retained sufficient protease activity and, moreover, its calcium-sensitivity was higher than that of intact muCANP. The possibility is thus proposed that restricted autodigestion is a necessary activation step for the appearance of activity of muCANP. No such transition was observed for mCANP.
 ...
PMID:Hydrolytic and autolytic behavior of two forms of calcium-activated neutral protease (CANP). 299 95

FOR MANY DECADES TWO TYPES OF ACUTE PANCREATITIS HAVE BEEN RECOGNIZED: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary alpha-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess.
 ...
PMID:Acute pancreatitis. 455 67

A Sarcina strain (Coccus P) produces two proteolytic enzymes. One is found only extracellularly, is far more prevalent, and is actively excreted during exponential growth. It is the enzyme responsible for the known strong proteolytic activity of the cultures of this strain. A second protease is, however, produced which remains associated with the intact cells but is released by the protoplasts. The two enzymes appear unrelated in their derivation. Calcium ions play an essential role in preventing autodigestion of the excreted enzyme.
 ...
PMID:Mechanism of excretion of a bacterial proteinase: demonstration of two proteolytic enzymes produced by a Sarcina strain (Coccus P). 510 56

Low and high Ca2+-requiring forms of Ca2+-dependent cysteine proteinase are known as calpain I and calpain II, respectively. We have obtained, for the first time, monospecific antibodies for calpain I and for calpain II. Using these antibodies and an electrophoretic blotting method, we have found that a small, but reproducible, amount of calpain I was associated with human erythrocyte membranes while the bulk of the protease was contained in the cytosol. Most of membrane-associated calpain I was extractable with 1% Triton X-100, but not with 0.1% detergent. In the presence of 0.1 mM Ca2+ and 5 mM cysteine, membrane-associated calpain I degraded the membrane protein band 4.1 preferentially and band 3 protein only slowly. The Ca2+-induced autodigestion of the membrane preparation was inhibited by leupeptin but not by a cytosolic calpain inhibitor, calpastatin, added to the incubation medium. No calpain II was detected in either erythrocyte cytosol or membranes when anti-calpain II antibody was used under the same conditions as those for the detection of calpain I.
 ...
PMID:Evidence for membrane-associated calpain I in human erythrocytes. Detection by an immunoelectrophoretic blotting method using monospecific antibody. 608 91

Proteolytic cleavage of lexA repressor is an early step in derepression of the SOS regulatory system of Escherichia coli. In vivo and in vitro data have indicated a role for recA protein in this specific proteolytic reaction. I show here that, under certain conditions, specific in vitro cleavage of highly-purified lexA protein can take place in the absence of recA protein. This autodigestion reaction cleaved the same alanine-glycine bond as did the recA-dependent cleavage reaction. Several lines of evidence argued that it was not due to a contaminating protease activity. Autodigestion was stimulated by alkaline pH. It occurred in the presence of EDTA but was stimulated several fold by the presence of Ca2+, Co2+, or Mg2+. The reaction appeared to be first-order, and its rate was independent of protein concentration over a wide range, strongly suggesting that it is intramolecular. Purified phage lambda repressor also broke down under similar conditions to yield products like those resulting from recA protein action. Phage lambda repressor broke down at a far slower rate than did lexA, as previously observed in the recA-catalyzed in vitro reaction and in vivo. This correlation between the two types of cleavage also extended to the reactions with mutant repressor proteins; taken together with the site specificity, it suggests that autodigestion and recA-dependent cleavage follow, at least in part, a similar reaction pathway. These findings indicate that specific cleavage of lexA protein can be catalyzed by the protein itself and suggest that recA protein plays an indirect stimulatory role, perhaps as an allosteric effector, in the recA-dependent reaction, rather than acting directly as a protease. The protease active site and the recA-recognition site lie in the central or COOH-terminal portion of the lexA protein, since a tryptic fragment containing these portions of lexA protein could take part in both reactions.
 ...
PMID:Autodigestion of lexA and phage lambda repressors. 623 41

The degradation of vimentin and desmin by the Ca2+-activated proteinase specific for these intermediate filament proteins proceeds in two stages in the form of a limited proteolysis. At first, the reaction is very rapid, with the stepwise and complete removal of a peptide (ca. 9,000 daltons) from the N-terminal of vimentin and desmin. This results in the production of a characteristic "staircase" of degradation products, as seen in two-dimensional polyacrylamide gel electrophoresis. The second stage of proteolysis is characterized by the accumulation of peptides which are resistant to further proteolysis; this is due not to product inhibition but to the fact that these peptides are not substrates for the proteinase and therefore do not protect the latter from inactivation (autodigestion). In vitro phosphorylation of the substrates does not affect proteinase activity, probably because the phosphorylation site is located towards the C-terminal of the molecules. The specific and limited proteolysis of vimentin and desmin results in the deletion of the nucleic acid binding and filament assembly site of these proteins, indicating that the Ca2+-activated proteinase plays a role in regulating the function(s) of these intermediate filament proteins, rather than their simple turnover during the cell cycle.
 ...
PMID:Proteolysis of vimentin and desmin by the Ca2+-activated proteinase specific for these intermediate filament proteins. 630 28

A simple method avoiding the use of nonionogenic detergent has been developed for the isolation of two forms of boar acrosin from ejaculated sperm. Each of the two forms was electrophoretically homogeneous and showed one N-terminal sequence only; Val-Val. The two acrosin forms isolated differ in molecular mass and amino acid composition. alpha-Acrosin, the form showing a higher molecular mass (Mr approximately 50 000), is stable in acid media. When exposed to pH above 4 it is converted into beta-acrosin (Mr approximately 35 000) by autodigestion. The isolation of the alpha-form was therefore carried out below pH 4 to eliminate autodigestion to the beta-form. The beta-form is stable for a certain period at neutral pH, especially if stabilized by Ca2+ ions. The autodigestion of alpha-acrosin to beta-acrosin probably results in the liberation of the C-terminal portion of the molecule of the alpha-form; this portion is composed of roughly 85 residues and is rich in proline.
 ...
PMID:Boar acrosin. Isolation of two active forms from boar ejaculated sperm. 675 82


1 2 3 Next >>