Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leupeptin, chymostatin and antipain inhibited the degradation of long-lived proteins in cultured rat hepatocytes by 20-30%, probably by inhibiting lysosomal proteases: (1) Leupeptin and chymostatin decreased to a similar extent the degradation of an exogenous protein 125I-asialo fetuin, a process known to occur within lysosomes. (2) In extracts of cells treated with leupeptin, cathepsin B activity was inhibited by 35-50%. (3) Leupeptin, chymostatin and antipain inhibited proteolysis by homogenates of liver lysosomes but not by the supernatant fraction. These agents, however, do not appear to rapidly permeate the membrane of isolated lysosomes. Leupeptin, chymostatin and antipain did not inhibit the breakdown of short-lived normal cell proteins, and ones containing amino acid analogs. Even when the amount of abnormal proteins was increased, such that it comprised a large fraction of cell protein, the degradation of these polypeptides was still very rapid and not affected by these inhibitors. The pathway for the degradation of short-lived cell proteins thus appears distinct from that responsible for degradation of long-lived cell proteins. In accord with this conclusion, reduction of the temperature of cultures inhibited the breakdown of long-lived proteins to a much greater extent than it affected the breakdown of short-lived ones. Treatment of cultured hepatocytes with glucagon, or deprivation for serum or amino acids stimulated the degradation of the more stable cell proteins but did not affect the breakdown of 125I-asialo-fetuin. Under these conditions leupeptin and chymostatin inhibited the breakdown of long-lived cell proteins to the same extent as in control cultures. Thus, lysosomal enzymes seem to play an important role in protein breakdown both in fed hepatocytes and in cells where proteolysis is accelerated.
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PMID:The effect of protease inhibitors and decreased temperature on the degradation of different classes of proteins in cultured hepatocytes. 52 71

The acid saline extract (ASE) of rat submaxillary gland exerts a powerful degrading effect on 125I-glucagon. In order to study the degradation of other 125I-peptides by ASE and the effects of their inhibitors, 125I-pancreatic polypeptide (PP) and 125I-insulin were used together with 125I-glucagon. The degradation studies were done by the trichloroacetic acid (TCA) method or gel filtration. Besides 125I-glucagon, 125I-PP was found to be destroyed by ASE in the ordinary immunoassay system using the TCA method, but 125I-insulin was intact in the presence of ASE. Leupeptin, and to a lesser extent p-chloromercuriphenyl-sulfonic acid (PCMS) and N-ethylmaleimide, inhibited the destruction of 125I-glucagon or -PP under the TCA method. PCMS was especially protective at high concentrations, for example 16 mM. These findings were confirmed by gel filtration of the assay mixture. In the presence of leupeptin (0.4 mM) and PCMS (16 mM), no shift in the peak of labelled glucagon or PP occurred. Thus ASE degrades not only 125I-glucagon but -PP, and thiol proteinase inhibitors have a strong inhibitory action on them.
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PMID:Degradation of 125I-glucagon, -pancreatic polypeptide and -insulin by acid saline extract of rat submaxillary gland and their protection by proteinase inhibitors. 254 48

1. Rat intestinal smooth muscle was shown to contain endogenous inhibitory activity towards the neutral trypsin-like muscle proteinase described previously [Beynon & Kay (1978) Biochem. J. 173, 291--298]. 2. Comtamination of the muscle tissue by mucosal, blood and pancreatic inhibitors was shown to be unlikely. 3. The inhibitory activity was resolved into high- and low-molecular-weight components. 4. The low-molecular-weight component was purified to homogeneity. It has a molecular weight of approx. 9000 and was stable over the pH range 3--11. 5. It inhibited the muscle proteinase competitively (Ki congruent to t microM), but had no effect on any of the other proteinases tested. 6. Leupeptin also inhibited the muscle proteinase competitively (Ki congruent to 0.3 microM), whereas the low-molecular weight proteins gastrin, glucagon and insulin B-chain had very little effect. 7. A role for a weakly binding inhibitor in modulating the influence of the neutral proteinase on intracellular protein degradation is considered.
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PMID:A low-molecular-weight inhibitor of the neutral proteinase from rat intestinal smooth muscle. 739 24