Up‐Regulation of Cytochrome P450 1A2, 2C9, and 2E1 in Chronic Pancreatitis

  title={Up‐Regulation of Cytochrome P450 1A2, 2C9, and 2E1 in Chronic Pancreatitis},
  author={Rainer Wacke and A Kirchner and Friedrich Prall and Horst Nizze and Wolfgang Schmidt and U Fischer and F P Nitschke and Ulrich Adam and Peter Fritz and C. Belloc and Bernd Drewelow},
The oxidative metabolism of xenobiotics is effected mainly by cytochrome P450 enzymes (CYP), which are expressed as a family of genetically related enzymes primarily in hepatocytes. The pancreas is among the extrahepatic tissues expressing CYP, and it has been suggested that intermediates generated by them might be of pathogenetic significance for diseases of the pancreas such as chronic pancreatitis. We studied 10 surgical resection specimens by immunohistochemistry with polyclonal antibodies… 

Differences in Immunohistochemical Expression of Xenobiotic-Metabolizing Enzymes Between Normal Pancreas, Chronic Pancreatitis and Pancreatic Cancer

Considering immunohistochemical evidence of enzyme expression and pancreatic blood supply together, islet cells appear to be an important and possible early site of CYP-enzyme induction in pancreatic diseases.

The Pattern of Xenobiotic-Metabolizing Enzymes in the Human Pancreas

An overall look at the distribution of the phase I xenobiotic-metabolizing enzymes, which are responsible for the metabolism of many common environmental toxins and carcinogens, in the normal pancreas shows that islet cells play a major role in the detoxification process of the Pancreas.

Polymorphisms of UDP-glucuronosyltransferase 1A7 are not involved in pancreatic diseases

The data suggest that, in contrast to earlier studies, UGT1A7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.

Functional polymorphisms of UDP-glucuronosyltransferases 1A1, 1A6 and 1A8 are not involved in chronic pancreatitis.

The data suggest that genetic polymorphisms in UGT1A1, UGT2A6 and in U GT1A8 do not predispose to the development of CP in Caucasians, and the distribution of the various alleles did not differ between CP patients and healthy controls.

Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzymes involved in alcohol metabolism.

In mice, the Aldh2 protein was detected in the liver, lung, heart, kidney, testis, esophagus, stomach, colon, and pancreas, suggesting that the tissue-distribution in mice is similar to that in humans, and suggests that a metabolite(s) of Aldh 2 might down-regulate the expression of Cyp2e1 gene.

Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas

The results imply a greater importance of the islet cells in the metabolism of xenobiotics within the pancreas than previously thought, and call for caution when extrapolating experimental results to humans.

Expression of Multidrug Resistance Proteins in Rat and Human Chronic Pancreatitis

The expression of P-gp and related transporters could have impact on the metabolism, distribution, and availability of various compounds, including drugs, in the pancreas and the results indicate that this could be more pronounced in chronic pancreatitis.

Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue.

It is shown that human prostate tissue can metabolically activate 'cooked meat' carcinogens, a process that could contribute to prostate cancer development.

Reappraisal of xenobiotic-induced, oxidative stress-mediated cellular injury in chronic pancreatitis: a systematic review.

Pancreatic acinar cell injury due to short-lived oxygen free radicals (generated by injury mediated by prematurely activated intra-acinar trypsin) is an important mechanism of cell damage in chronic pancreatitis, however, this should be seen as one of a series of cell-injury mechanisms rather than a sole mediator.



Induction of cytochromes P-450 in pancreatic disease: consequence, coincidence or cause?

Induction of drug‐metabolizing enzymes in human pancreatic cancer and chronic pancreatitis

The present findings raise the possibility of an aetiological relationship between elevated levels of drug‐metabolizing enzymes and the subsequent development of disease.

Smoking and peripheral type of cancer are related to high levels of pulmonary cytochrome P450IA in lung cancer patients

The data suggest that the smokers who have an inducible cytochrome P450IA are especially at increased risk of developing lung cancer of the peripheral adenocarcinomatous type.

Regiospecific expression of cytochrome P-450s and microsomal epoxide hydrolase in human brain tissue.

The results indicate that many neurons and astrocytes express mEH and CYP1A1 as well as other CYP genes, and suggest that localized biotransformation events within the certain central nervous system may account for toxicities initiated by exposure to certain environmental chemicals.

The immunocytochemical localisation and distribution of cytochrome P-450 in normal human hepatic and extrahepatic tissues with a monoclonal antibody to human cytochrome P-450.

Strong and weak immunoreactivity was identified in hepatocytes, columnar absorptive epithelial cells of the small intestine, polymorphonuclear leucocytes and their precursors in the bone marrow, and in mast cells, and Immunoreactivity could not be demonstrated in the adrenal gland, placenta, colonic epithelium and alveolar type II cells and Clara cells ofThe lung.

Factors contributing to the accelerated clearance of theophylline and antipyrine in adults with exocrine pancreatic disease.

The lack of correlation between pancreatic secretory capacity in 56 cases, judged by a secretin-pancreozymin test, and theophylline clearance suggests that enzyme induction is not secondary to pancreatic dysfunction, and suggests that enzymes induction in pancreatic disease preferentially involves the polycyclic aromatic hydrocarbon-inducible subfamily of cytochrome P-450.

3-Methylcholanthrene and pyridine effects on CYP1A1 and CYP1A2 expression in rat renal tissue.

Results show that expression of CYP1A1 and 1A2 mRNAs is enhanced in renal tissue after exposure to 3-MC or pyridine, and that constitutive expression of cyclic cytochrome P450 seems to be greater than that of CYp1A2 in kidney tissue.

Acetone-dependent regulation of cytochrome P-450j (IIE1) and P-450b (IIB1) in rat liver.

P450 IIE1 is catalytically inactivated in microsomes prior to the degradation of this protein, and Quantification of the proteins in lysosomes indicated that both P450 IIB1 and P450E1 are degraded via an autophagosomal/autolysosomal pathway.