PubMed Health⌕ Search

Biomedical subjects

Roger Harrison

Publications and source records attributed to Roger Harrison.

8 recordsLinked to original sources
PubMed2004

Xanthine oxidoreductase is present in bile ducts of normal and cirrhotic liver.

Xanthine oxidoreductase (XOR) is a widely distributed enzyme, involved in the metabolism of purines, which generates superoxide and is thought to be involved in free radical-generated tissue injury. It is present at high concentrations in the liver, from where it may be released during liver injury into the circulation, binding to vascular endothelium and causing vascular dysfunction. The cellular localization of the enzyme, essential to understanding its function, is, however, still debated. The present study has used a highly specific mouse monoclonal antibody to define the cellular distribution of XOR in normal and cirrhotic human liver. As shown previously, XOR is present in hepatocytes. However, the novel finding of this study is that XOR is present in bile duct epithelial cells, where it is concentrated toward the luminal surface. Moreover, in liver disease, proliferating bile ducts are also strongly positive for XOR. These findings suggest that the enzyme is secreted into bile, and this was confirmed by analysis of human and rat bile. Xanthine oxidase activity was 10 to 20-fold higher in liver tissue obtained from patients with liver disease, than in healthy liver. We conclude that XOR is expressed primarily in hepatocytes, but is also present in bile duct epithelial cells and is secreted into bile. Its role in bile is unknown but it may be involved in innate immunity of the bowel muscosa.

Animals↗
PubMed2004

Goats' milk xanthine oxidoreductase is grossly deficient in molybdenum.

Xanthine oxidoreductase (XOR) was purified from goats' milk. The u.v.-visible absorption spectrum was essentially identical to those of the corresponding bovine and human milk enzymes and showed an A280/A450 ratio of 5.20+/-0.12, indicating a high degree of purity. Like bovine and human milk XORs, enzyme purified from goats' milk showed a single band on SDS-PAGE corresponding to a subunit with approximate Mr 150,000. On Western blotting, mouse monoclonal anti-human XOR antibody cross-reacted with purified caprine and bovine XORs. The specific xanthine oxidase activity of goats' milk XOR, however, was very much lower than that of bovine XOR, although NADH oxidase activities of XOR from the two sources were similar. In these respects, the caprine milk XOR mirrors the human milk enzyme, in which case the kinetic effects have previously been attributed to relatively low molybdenum content. The molybdenum content of goats' milk XOR also was shown to be relatively low, with 0.09 atoms Mo per subunit, compared with 055 atoms Mo per subunit for the bovine enzyme. A parallel purification of human milk XOR showed 0.03 atoms Mo per subunit. The possible physiological significance of the low molybdenum content of the caprine milk enzyme and of its correspondingly low enzymic activity is discussed.

Animals↗
PubMed2004

Physiological roles of xanthine oxidoreductase.

Xanthine oxidoreductase (XOR) is a major protein component of the milk fat globule membrane (MFGM) surrounding fat droplets in milk and its enzymology is well characterised. The enzyme is widely distributed in mammalian tissues and is generally accepted to be a key enzyme of purine catabolism. It catalyses the oxidation of a wide range of substrates and can pass electrons to molecular oxygen, generating reactive oxygen species (ROS); similar reduction of nitrite yields reactive nitrogen species (RNS). While XOR has been implicated in ischemia-reperfusion injury, its involvement in normal physiological processes has been less studied. It is argued here that XOR-derived ROS and RNS play a role in innate immunity, specifically in the inflammatory response and in anti-microbial defense of the gastrointestinal tract. XOR-derived species could also be involved in signalling. Additionally, XOR is likely to play a part in metabolism of xenobiotics and has recently been shown to mediate the secretion of milk fat globules. The human enzyme has only relatively recently been characterized. The enzyme purified from breast milk shows very low enzymatic activity, and it is suggested that human XOR has evolved so as to be regulated by an exceptional range of pre- and posttranslational mechanisms.

Animals↗
PubMed2002

Structure and function of xanthine oxidoreductase: where are we now?

Xanthine oxidoreductase (XOR) is a complex molybdoflavoenzyme, present in milk and many other tissues, which has been studied for over 100 years. While it is generally recognized as a key enzyme in purine catabolism, its structural complexity and specialized tissue distribution suggest other functions that have never been fully identified. The publication, just over 20 years ago, of a hypothesis implicating XOR in ischemia-reperfusion injury focused research attention on the enzyme and its ability to generate reactive oxygen species (ROS). Since that time a great deal more information has been obtained concerning the tissue distribution, structure, and enzymology of XOR, particularly the human enzyme. XOR is subject to both pre- and post-translational control by a range of mechanisms in response to hormones, cytokines, and oxygen tension. Of special interest has been the finding that XOR can catalyze the reduction of nitrates and nitrites to nitric oxide (NO), acting as a source of both NO and peroxynitrite. The concept of a widely distributed and highly regulated enzyme capable of generating both ROS and NO is intriguing in both physiological and pathological contexts. The details of these recent findings, their pathophysiological implications, and the requirements for future research are addressed in this review.

Animals↗