Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported that serum hepatocyte growth factor (HGF) levels are elevated in patients with acute pancreatitis and that pancreatitis-associated ascitic fluid (PAAF) contains cytotoxic factor(s) inducing apoptosis on Madin-Darby canine kidney (MDCK) cells. In this study, plasma HGF levels and HGF tissue distribution were investigated in rats with experimental acute pancreatitis, and the effects of HGF on the cytotoxic activity and apoptosis-inducing activity of PAAF also were examined. Plasma HGF levels were elevated in rats with two experimental pancreatitis models of different grades of severity. The degree of its elevation was correlated with the severity and the organ dysfunctions. In rats with severe pancreatitis, HGF protein and messenger RNA (mRNA) levels significantly increased in liver, kidney, and lung, which were injured organs. When anti-HGF neutralizing antibody was administered in severe pancreatitis, liver dysfunction worsened, and apoptotic cells increased in kidney. Recombinant HGF inhibited the cytocidal activity of PAAF on MDCK cells in a dose-dependent manner. Moreover, recombinant HGF prevented the apoptotic cell death (DNA fragmentation, nuclear fragmentation, and caspase-3 activation) induced by PAAF. These results suggest that HGF is produced in injured organs and may function as an organotrophic and antiapoptotic factor against the organ injuries in acute pancreatitis.
Pancreas 2000 Jan
PMID:Hepatocyte growth factor increases in injured organs and functions as an organotrophic factor in rats with experimental acute pancreatitis. 1063 Mar 88

The purpose of this study was to determine if alcohol consumption and endotoxin injection change the rate of apoptosis in the pancreas. Rats were fed a Lieber-DeCarli diet for 14 weeks. At 14 weeks, the animals were injected with lipopolysaccharide (LPS) or saline and killed. The pancreata were resected and snap frozen. Apoptosis was detected by TUNEL assay. Caspase-3 activity, Bcl-2 (protein), and Fas ligand (mRNA) were assayed in pancreas extracts and alpha-amylase in plasma. Alcohol feeding significantly decreased alpha-amylase and caspase-3 activity, and significantly increased Bcl-2. LPS injection increased caspase-3 activity and decreased Bcl-2. Fas ligand mRNA was increased only in alcohol-fed, LPS-injected rats. TUNEL labeling was significantly increased only in alcohol-fed, LPS-injected rats. These data show that (a) long-term alcohol feeding suppresses apoptosis in the pancreas; (b) LPS increases the rate of apoptosis in the pancreas; (c) caspase-3 activity and Bcl-2 expression change in opposite directions; (d) TUNEL positivity and Fas ligand expression are increased, and Bcl-2 is decreased in ethanol-fed + LPS-injected rats. These results suggest that prolonged alcohol consumption may sensitize acinar cells to endotoxin-induced injury and raise the possibility that a similar mechanism may cause pancreatitis in human alcoholics.
Pancreas 2000 Aug
PMID:Alcohol feeding and lipopolysaccharide injection modulate apoptotic effectors in the rat pancreas in vivo. 1097 12

Caspase-3/CPP32, a member of the Ced-3-family of cysteine proteases, is an important mediator of programmed cell death (apoptosis). Intraductal papillary-mucinous tumor of the pancreas (IPMT) is a unique tumor that grows intraductally with rare stromal invasion. However, it is not possible to distinguish noninvasive from invasive IPMT preoperatively. To examine whether caspase-3 expression reflects the biological behavior of pancreatic tumors, we investigated this enzyme expression by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in 22 pancreatic duct cell carcinomas (PDC) and 13 IPMT cases. Caspase-3 mRNA was overexpressed in PDC and IPMT with carcinoma when compared with normal pancreatic tissue or IPMT with adenoma. The immunoreactivity of this enzyme was predominantly found in the cytoplasm of invasive tumors (PDC and invasive IPMT). There was a significant correlation between the cytoplasmic staining and malignant grade of the tumors. In contrast, the nuclear expression of this enzyme was significantly higher in noninvasive than in invasive tumors (p = 0.0015). Cytoplasmic expression of caspase-3 may be related to the invasiveness of pancreatic tumors. In contrast, nuclear expression of this enzyme may reflect the benign biological behavior of IPMT.
Pancreas 2000 Nov
PMID:The pattern of CPP32/caspase-3 expression reflects the biological behavior of the human pancreatic duct cell tumors. 1107 89

In the present study we investigated the intracellular signaling pathway leading to p53-independent activation of caspase-3 during heat-induced apoptosis of pancreatic carcinoma cells. Induction of mutant p53 protein, but not p21/WAF-1, was observed after heat treatment of both heat-resistant (PANC-1) and heat-sensitive (MIAPaCa-2) cells. A specific inhibitor of caspase-3 (Ac-DMQD-CHO) caused 84% and 92% inhibition of apoptosis in MIAPaCa-2 and PANC-1 cells, respectively. Caspase-3 mRNA expression was increased in both cell lines after heat treatment. Further, heat-induced caspase-3 activity detected by fluorogenic assay in MIAPaCa-2 cells was almost completely inhibited by addition of the antioxidant N-acetyl-L-cysteine. In contrast, Ac-DMQD-CHO had no inhibitory effect on amounts of reactive oxygen species in heat-treated MIAPaCa-2 cells. These results suggest a possible pathway by which reactive oxygen species lead to caspase-3 activation to cause heat-induced death of pancreatic carcinoma cells carrying mutant p53.
Pancreas 2001 Apr
PMID:Caspase-3 activation downstream from reactive oxygen species in heat-induced apoptosis of pancreatic carcinoma cells carrying a mutant p53 gene. 1129 26

We have previously shown that arsenic trioxide blocks proliferation and induces apoptosis in human pancreatic cancer cells at low, non-toxic concentrations. The mechanisms of the apoptosis was investigated in MiaPaCa2 and PANC-1 cells that have been previously shown to be responsive to arsenic trioxide. The results show the caspase-3, caspase-7, and caspase-9 are all activated by arsenic trioxide, together with cleavage of the downstream caspase-3 target poly ADP ribose polymerase (PARP). Expression of the anti-apoptosis proteins, Bcl-2 and Mcl-1 expression decreased time-dependently while Bax expression increased. These findings indicate that the Bcl family of proteins, the mitochondrial pathway and activation of the caspase cascade are responsible for arsenic-induced apoptosis. Flow cytometric analysis revealed changes of cell cycle distribution from a G0/G1 phase arrest at 24 hours to G2/M phase arrest at 72 hours following arsenic treatment. The sub-G0/G1 cell population of apoptotic cells was increased at these times. Arsenic increased expression of the P21 protein and decreased levels of cyclin A, cyclin B1 and cyclin D1, but expression of CDK2, CDK4, CDK6, and cyclin E were not affected. Arsenic trioxide markedly enhanced the expression of GADD45 and GADD153 in a time-dependent manner. In summary, arsenic trioxide induced apoptosis in pancreatic cancer cells through activating the caspase cascade via the mitochondrial pathway, GADD expression and by modifying cell cycle progress and changes in several cycle-regulating proteins. This old drug may be valuable for treatment of pancreatic cancer.
Pancreas 2003 Aug
PMID:Arsenic trioxide induces apoptosis in pancreatic cancer cells via changes in cell cycle, caspase activation, and GADD expression. 1288 67