Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xanthine dehydrogenase (XDH) is an important precursor to the oxygen radical producing enzyme xanthine oxidase (XO). We found that the apparent activity of rabbit myocardial XDH increased from 2 +/- 1 to 50 +/- 3 microU/g (P < 0.05) following extraction of tissue homogenate with butanol. Further studies suggested that the basis for this observation was a high molecular weight compound which consumes the XDH cofactor, NAD+. Addition of myocardial homogenate to exogenous NAD+ resulted in depletion of NAD+ and concomitant formation of an additional compound (peak A). Both NAD+ consumption and peak A formation were abrogated by prior extraction of homogenate with butanol. Separation of myocardial homogenate by Sephadex chromatography revealed a high molecular weight compound which suppressed activity of purified milk XDH but not xanthine oxidase (XO). This activity co-eluted with the ability of myocardial homogenate to consume added NAD+ and form peak A. The NAD(+)-consuming activity was heat and acid-labile. In addition, nicotinamide was both a product and an inhibitor of the NADase activity, consistent with the existence of a previously described myocardial glycohydrolase. Extraction of tissue with butanol may be necessary to detect low levels of XDH activity in vitro.
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PMID:Suppression of rabbit myocardial xanthine dehydrogenase activity by an endogenous compound. 800 74

Recent studies in our lab and by others have indicated that cyclic ADP-ribose (cADPR) as a novel second messenger is importantly involved in vasomotor response in various vascular beds. However, the mechanism regulating cADPR production and actions remains poorly understood. The present study determined whether changes in redox status influence the production and action of cADPR in coronary arterial smooth muscle cells (CASMCs) and thereby alters vascular tone in these arteries. HPLC analyses demonstrated that xanthine (X, 40 microM)/xanthine oxidase (XO, 0.1 U/ml), a superoxide-generating system, increased the ADP-ribosyl cyclase activity by 59% in freshly isolated bovine CASMCs. However, hydrogen peroxide (H2O2, 1-100 microM) had no significant effect on ADP-ribosyl cyclase activity. In these CASMCs, X/XO produced a rapid increase in [Ca2+]i (Delta[Ca2+]i=201 nM), which was significantly attenuated by a cADPR antagonist, 8-Br-cADPR. Both inhibition of cADPR production by nicotinamide (Nicot) and blockade of Ca2+-induced Ca2+ release (CICR) by tetracaine (TC) and ryanodine (Rya) significantly reduced X/XO-induced rapid Ca2+ responses. In isolated, perfused, and pressurized small bovine coronary arteries, X at 2.5-80 microM with a fixed XO level produced a concentration-dependent vasoconstriction with a maximal decrease in arterial diameter of 45%. This X/XO-induced vasoconstriction was significantly attenuated by 8-Br-cADPR, Nicot, TC, or Rya. We conclude that superoxide activates cADPR production, and thereby mobilizes intracellular Ca2+ from the SR and produces vasoconstriction in coronary arteries.
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PMID:Enhanced production and action of cyclic ADP-ribose during oxidative stress in small bovine coronary arterial smooth muscle. 1502 Feb 7