The Activation of Trypsinogen by Cathepsin B

Greenbaum, Lowell M.; Hirshkowitz, A.; Shoichet, Irving

doi:10.1016/s0021-9258(18)69688-7

Cited by 113 publications

(12 citation statements)

References 13 publications

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“…Some of these effects may be due to universal mechanisms of cell metabolism regulation by NO such as tonic modulation of cell respiration and inhibition of caspases. NO was also reported to inhibit cathepsin B (Stamler et al 1992), which may mediate intrapancreatic trypsinogen activation (Greenbaum et al 1959;Halangk & Lerch 2004) and lead to AP. The stimulatory effect of NO on exocytosis may also exert a beneficial action on the cells, since inhibition of secretion is associated with pancreatic acinar cell pathology (Lerch & Adler 1994; figure 1).…”

Section: No Links To Pancreatic Acinar Cell Homeostasis and Pathologymentioning

confidence: 99%

Free radicals and the pancreatic acinar cells: role in physiology and pathology

Chvanov

Petersen

Tepikin

2005

Phil. Trans. R. Soc. B

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Reactive oxygen and nitrogen species (ROS and RNS) play an important role in signal transduction and cell injury processes. Nitric oxide synthase (NOS)-the key enzyme producing nitric oxide (NO)-is found in neuronal structures, vascular endothelium and, possibly, in acinar and ductal epithelial cells in the pancreas. NO is known to regulate cell homeostasis, and its effects on the acinar cells are reviewed here. ROS are implicated in the early events within the acinar cells, leading to the development of acute pancreatitis. The available data on ROS/RNS involvement in the apoptotic and necrotic death of pancreatic acinar cells will be discussed.

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Section: No Links To Pancreatic Acinar Cell Homeostasis and Pathologymentioning

confidence: 99%

Free radicals and the pancreatic acinar cells: role in physiology and pathology

Chvanov

Petersen

Tepikin

2005

Phil. Trans. R. Soc. B

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“…The question remains as to how the activation of trypsinogen is initiated. Previous investigators have speculated that intracellular colocalization of lysosomal enzymes and trypsinogen may be the initiating event because previous studies have demonstrated the capability of cathepsin B to activate trypsinogen in vitro (11,15). In accordance with other reports, no significant changes of enzyme distribution were induced by infusion of saline or 0.25 µg • kg Ϫ1 •h Ϫ1 caerulein ( 43), but during caerulein hyperstimulation there was a continuous increase of cathepsin B activity in the ZRF and PMF in parallel with a relative decrease of its activity in the LRF.…”

Section: G75 Trypsinogen and Lysosomal Enzymes In Acute Pancreatitismentioning

confidence: 99%

“…Subcellular fraction-ation techniques demonstrated a coincident increase of lysosomal enzyme activity in the zymogen compartment, which includes crinophagic vacuoles (29,43,56). Because previous studies have demonstrated the capability of the lysosomal enzyme cathepsin B to activate trypsinogen in vitro (11,15), it has been suggested that such an intracellular admixture of cathepsin B and trypsinogen may cause intracellular activation of trypsinogen (43,49,50,54). Inasmuch as trypsin triggers the activation of the pancreatic enzyme cascade (40), it is speculated that cathepsin B-induced intracellular trypsinogen activation may be an early event in the pathophysiological processes leading to autodigestion of the gland (43,50).…”

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confidence: 98%

Subcellular kinetics of early trypsinogen activation in acute rodent pancreatitis

Mithöfer

Castillo

Rattner

et al. 1998

American Journal of Physiology-Gastrointestinal and Liver Physi

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To investigate the debated role of intracellular trypsinogen activation and its relation to lysosomal enzyme redistribution in the pathogenesis of acute pancreatitis, rats were infused with the cholecystokinin analog caerulein at 5 μg ⋅ kg−1 ⋅ h−1for intervals up to 3 h, and the changes were contrasted with those in animals receiving saline or 0.25 μg ⋅ kg−1 ⋅ h−1caerulein. Saline or 0.25 μg ⋅ kg−1 ⋅ h−1caerulein did not induce significant changes. In contrast, 5 μg ⋅ kg−1 ⋅ h−1caerulein caused significant hyperamylasemia and pancreatic edema within 30 min. Pancreatic content of trypsinogen activation peptide (TAP) increased continuously (significant within 15 min). TAP generation was predominantly located in the zymogen fraction during the first hour but expanded to other intracellular compartments thereafter. Cathepsin B activity in the zymogen compartment increased continuously throughout the experiments and correlated significantly with TAP generation in the same compartment. Total trypsinogen content increased to 143% with marked interstitial trypsinogen accumulation after 3 h. Supramaximal caerulein stimulation causes trypsinogen activation by 15 min that originates in the zymogen compartment and is associated with increasing cathepsin B activity in this subcellular compartment. However, a much larger pool of trypsinogen survives and accumulates in the extracellular space and may become critical in the evolution of necrotizing pancreatitis.

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“…However, neither cathepsin D nor cathepsin A is influenced by sulfhydryl compounds. Accordingly, enhancement of autolytic reactions by thiols probably reflects activities of cathepsins B and C. Greenbaum et al (1959) have shown that partially purified preparations of cathepsin B hydrolyze proteins, whereas other workers (Planta et al, 1964) report cathepsin C to be devoid of proteolytic activity. Moreover, Ali (1964, 1967 and Ali et al (1967) have implicated cathepsin B in the autolytic degradation of cartilage matrix.…”

Section: Discussionmentioning

confidence: 98%

Autolytic activity in aqueous extracts of chicken skeletal muscle

Caldwell¹

1970

J. Agric. Food Chem.

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Autolytic changes in extracts of chicken skeletal muscle at 37°C have been investigated by measuring changes in acid soluble tyrosine equivalents. Autolysis is maximal at pH 3. This activity is enhanced by cysteine and by other thiols; it is inhibited substantially by 6-aminocaproic acid, iodoacetamide, cyanide, and mercuric ions; it is inhibited slightly by zinc ions and essentially unaffected by EDTA, ferrous, magnesium, or calcium

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The Activation of Trypsinogen by Cathepsin B

Cited by 113 publications

References 13 publications

Free radicals and the pancreatic acinar cells: role in physiology and pathology

Free radicals and the pancreatic acinar cells: role in physiology and pathology

Subcellular kinetics of early trypsinogen activation in acute rodent pancreatitis

Autolytic activity in aqueous extracts of chicken skeletal muscle

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