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)

Cathepsins B and H are representative cysteine proteinases localized to lysosomes of a variety of mammalian cells. Previous studies indicated the presence of these enzymes also in secretory granules of endocrine cells. Therefore, the human endocrine pancreas and human insulinomas were investigated by light microscopical immunohistochemistry on serial semithin plastic sections immunostained sequentially for cathepsins B or H and pancreatic hormones. Out of the four established endocrine cell types, insulin (B-) and glucagon (A-) cells showed immunoreactivities for these cathepsins. Cathepsin B immunoreactivities showed a dot-like appearance in A- and B-cells and in insulinoma cells. Immunoreactivities for cathepsin H additionally were found in cell parts containing secretory granules of B-cells and insulinoma cells. By single and double immunoelectron microscopy the dot-like immunoreactivities for cathepsin B were identified as immunoreactive lysosomes of A- and B-cells and insulinoma cells. In addition, some of the secretory granules of A- and B-cells showed cathepsin B immunoreactivities. Cathepsin H immunoreactivities showed an other pattern: they were found regularly in the secretory granules of A- and B-cells and insulinoma cells, and in lysosomes of A-cells. These findings suggest that cathepsins B and H in lysosomes of A- and/or B-cells are involved in the degradation of lysosomal constituents. In secretory granules of these cells, these cysteine proteinases may participate in the processing of the corresponding hormones from their precursor proteins.
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PMID:Immunocytochemical localization of cathepsins B and H in human pancreatic endocrine cells and insulinoma cells. 255 67

To determine the characteristics of lysosomes in rat islet endocrine cells, we examined the precise localization of cathepsins B, H, and L and their specific inhibitors, cystatins alpha and beta, using immunocytochemical techniques. By use of serial semi-thin sections, we detected immunoreactivity for cathepsin B in insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-positive (PP) cells. Strong immunoreactivity for cathepsin H was seen in A-cells and weak immunoreactivity in PP cells, but none in others. Immunodeposits for cystatin beta were demonstrated in B-cells. Brief dipping of thin sections in 1% sodium methoxide before the following immunocytochemical reaction enhanced specific deposits of immunogold particles on the target organelles. Use of a double-immunostaining technique showed co-localization of insulin with cystatin beta in many secretory granules. This suggests that cystatin beta may regulate converting enzymes participating in the maturation process of insulin. By use of an immunogold technique, heterogeneous localization of cathepsins B and H in lysosomes was also found among islet cells at the light microscopic level. This may be due to the difference in peptides degraded in lysosomes among the cells.
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PMID:Immunocytochemical localization of cathepsins B, H, and their endogenous inhibitor, cystatin beta, in islet endocrine cells of rat pancreas. 329 Mar 33

In vivo proteolytic modification of liver aldolase on administration of leupeptin, a thiol proteinase inhibitor of microbial origin, is reported. When leupeptin was injected into rats, the activity of aldolase in the liver decreased to 40% of that in control rats. Molecular properties of aldolase isolated from the livers of control rats and leupeptin-treated rats indicated that a decrease of aldolase activity is attributable to hydrolysis of a peptide linkage(s) near the carboxyterminal of the enzyme. Injection of leupeptin also caused marked increase in the activities of free lysosomal proteinases, such as cathepsin A and cathepsin D and moderate increase of cathepsin B and cathepsin L. Increase in free activity of cathepsin A returned to the level of control rats by 12 hr after injection of leupeptin, whereas 36 hr was required for recovery of decreased aldolase activity. When insulin was coinjected with leupeptin, increase in the activity of free cathepsin A and decrease of activity of aldolase produced by the injection of leupeptin was prevented. These findings indicate that modification of aldolase may be due to action of a lysosomal protease(s). Incubation of the purified aldolase with the lysosomal fraction produced the same changes in properties of aldolase as those observed in vivo on injection of leupeptin. The aldolase inactivating proteinase in the lysosomal fraction was inhibited by PMSF and leupeptin and not by pepstatin. Purified cathepsin A (a serine proteinase), cathepsin B and cathepsin L (thiol proteinase) are potent inactivators of aldolase but cathepsin H and cathepsin D are not. Cathepsin A, B and L are involved in inactivation of aldolase in lysosomes. Endogenous thiol proteinase inhibitor which inhibits lysosomal thiol proteinases (cathepsin B, L and H) is found in the cytosol fraction of liver. The level of thiol proteinase inhibitor actually decreased to 60% of that in control rats in leupeptin-treated rats, suggesting that non-thiol proteinase cathepsin A is a major factor in inactivation of aldolase in lysosomes. Not only leupeptin but also other proteinase inhibitors (antipain, E-64-D, chloroquine) caused increase of labilization of the lysosomes and decrease in aldolase activity. Physiological stimuli which are known to induce the labilization of the lysosomal membrane, such as starvation and glucagon, caused slight or no significant increase of activities of free cathepsin A and D and resulted in no apparent change in aldolase activity.
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PMID:Modification of rat liver fructose biphosphate aldolase by lysosomal proteinases. 705 71