Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferation and matrix synthesis by activated pancreatic stellate cells (PSC) participate in the development of chronic pancreatitis. Apoptosis of PSC may terminate this process but has not yet been studied in this particular cell type and was the aim of the present study. PSC were isolated from rat pancreas and characterized for expression of glial fibrillary acidic protein, alpha-smooth muscle actin, CD95, and tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) receptors. Apoptosis was determined by TdT-UTP nick end-labeling reaction, annexin V binding, and caspase-8 activation. Both CD95L and TRAIL induced apoptosis in PSC. The apoptotic response was minor in PSC cultured for 7 days but increased markedly thereafter. Sensitization of PSC with culture duration was accompanied by increased expression of CD95 and TRAIL receptor 2 and no alterations of Flip expression or protein kinase B phosphorylation but was paralleled by the appearance of a COOH-terminal cleavage product of receptor-interacting protein. PSC apoptosis was also induced by PK-11195, a ligand of the peripheral benzodiazepine receptor. PSC apoptosis may be important in terminating the wound-healing response after pancreas injury and exhibits features distinct from apoptosis induction in hepatic stellate cells.
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PMID:Apoptosis in activated rat pancreatic stellate cells. 1218 Nov 99

Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to ethanol intragastrically (5 g/kg, 25% ethanol w/v) daily for 10 days. Binge ethanol exposure caused pathological changes in pancreas demonstrated by tissue edema, acinar atrophy and moderate fibrosis. Ethanol caused both apoptotic and necrotic cell death which was demonstrated by the increase in active caspase-3, caspase-8, cleaved PARP, cleaved CK-18 and the secretion of high mobility group protein B1 (HMGB1). Ethanol altered the function of the pancreas which was indicated by altered levels of alpha-amylase, glucose and insulin. Ethanol exposure stimulated cell proliferation in the acini, suggesting an acinar regeneration. Ethanol caused pancreatic inflammation which was indicated by the induction of TNF-alpha, IL-1beta, IL-6, MCP-1 and CCR2, and the increase of CD68 positive macrophages in the pancreas. Ethanol-induced endoplasmic reticulum stress was demonstrated by a significant increase in ATF6, CHOP, and the phosphorylation of PERK and eiF-2alpha. In addition, ethanol increased protein oxidation, lipid peroxidation and the expression of iNOS, indicating oxidative stress. Therefore, this paradigm of binge ethanol exposure caused a spectrum of tissue injury and cellular stress to the pancreas, offering a good model to study alcoholic pancreatitis.
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PMID:Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas. 2752 70