Immunohistochemical Localization of Xanthine Oxidase in Human Tissues.

Moriwaki, Yuji; Yamamoto, Tetsuya; Yamaguchi, Kensei; Suda, Michio; Yamakita, Jun-ichi; Takahashi, Sumio; Higashino, Kazuya

doi:10.1267/ahc.29.153

Cited by 7 publications

(8 citation statements)

References 28 publications

(32 reference statements)

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“…Immunoreactivities to p22 phox and gp91 phox are not detected in smooth muscle cells (a,b), whereas immunolabeling of smooth muscle cells (arrows) for p47 phox and p67 phox is evident in c and d. Their immunofluorescence causes a generally brighter image and, hence, shorter photographic exposure time that quenches documentation of autofluorescent lamellae in c and d. Bar 20 µm cells and smooth muscle cells of the same vessel. Xanthine oxidase, a prominent source of superoxide in several cell types (Jarasch et al 1981;Kooij et al 1992;Moriwaki et al 1996), has been reported to be absent from porcine PAEC (Yang and Block 1995), and its inhibition by allopurinol had no effect on the release of H 2 O 2 from bovine PAEC (Zuluetta et al 1995). Consistent with findings reported by Jones et al (1996) on HUVEC, detection of p22 phox -mRNA by RT-PCR was easier than for gp91 phox in that stronger signals were obtained for p22 phox .…”

Section: Rhodamine 123 Fluorescencesupporting

confidence: 80%

NADPH oxidase subunits and superoxide production in porcine pulmonary artery endothelial cells

Höhler

Holzapfel

Kummer

2000

Histochem Cell Biol

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An NADPH oxidase complex composed of a membrane-bound flavocytochrome b 558 consisting of two subunits (p22 phox and gp91 phox ) and cytosolic activating factors (p47 phox and p67 phox ) generates superoxide anions from oxygen in the respiratory burst of phagocytic cells. Inconsistent results have been previously obtained concerning its additional occurrence in pulmonary artery endothelial cells (PAEC), and this issue was addressed in the present study. PAEC isolated from porcine pulmonary trunk contained mRNA for p22 phox and gp91 phox as demonstrated by reverse transcription-polymerase chain reaction. Immunohistochemistry demonstrated cytochrome subunits, p22 phox , gp91 phox , p47 phox , and p67 phox , both in vitro in isolated PAEC and in situ in endothelial cells in tissue sections of the pulmonary trunk. Isolated PAEC generated reactive oxygen species (ROS; measured by lucigenin-induced chemiluminescence and conversion of dihydrorhodamine 123 into rhodamine 123) in response to stimulation with phorbol 12-myristate 13-acetate. This stimulated ROS production was sensitive to the flavoprotein inhibitor diphenyleneiodonium, and reduced when the superoxide scavenger superoxide dismutase was added. Chemiluminescence measurements of superoxide generation by stimulated PAEC accounted for approximately 1% of that generated by stimulated peritoneal macrophages. The data demonstrate a low-output NADPH oxidase system in porcine PAEC sharing several components with that identified in phagocytic cells.

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Section: Rhodamine 123 Fluorescencesupporting

confidence: 80%

NADPH oxidase subunits and superoxide production in porcine pulmonary artery endothelial cells

Höhler

Holzapfel

Kummer

2000

Histochem Cell Biol

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“…Both Moriwaki et al (1996) and Linder et al (1999) found that brain tissues were negative for XOR expression. In agreement, FANTOM5 human data showed no XDH expression in human brain samples (brain, adult samples: 0/2; Astrocyte-cerebellum: 0/3; Astrocyte-cerebral cortex: 0/3; cerebellum, adult 0/3; cerebral meninges: 0/1; hippocampus: 0/4; substantia nigra: 0/4), and all thirteen of GTEx Portal brain tissues had median TPM values of 0 or if expressed, were less than 0.5% that of liver.…”

Section: Cellular Energy-charge and Atp Turnovermentioning

confidence: 97%

“…While small-intestine was top ranked in human FANTOM5, in the mouse, intestinal mucosa had six times the relative expression levels compared to whole adult intestine, suggesting that expression is greater in certain intestinal cell subsets. Moriwaki et al (1996) found moderate to high levels of XOR in epithelium from various tissues including small and large intestine, trachea, bile duct, esophagus, tongue, breast mammary tissue, and lung bronchi. In human FANTOM5, 41% of human epithelial samples (30/73) expressed XDH , including a majority of bronchial (4/7) and all small-airway (3/3) epithelial samples.…”

Section: Cellular Energy-charge and Atp Turnovermentioning

confidence: 99%

“…Several lines of evidence can be used to understand the presence/absence of XOR in various human tissues and cell types. First, we examined results from several human immunohistochemistry (IHC) studies that investigated XOR protein localization using anti-XOR antibodies (Abs) (Hellsten-Westing, 1993; Moriwaki et al, 1996; Linder et al, 1999, 2005; Martin et al, 2004). Second, we analyzed gene expression data for XDH from the GTEx Portal browser 1 (Supplementary Table S1; n = 53; GTEx Consortium, 2017) and the FANTOM5 human Phase 1and 2 promoterome 2 (Supplementary Table S2; n = 1829; Hon et al, 2017; Lizio et al, 2015, 2017), and for comparison with a commonly analyzed model species, for mouse Xdh data from the Comprehensive Mouse Transcriptomic BodyMap 3 (Supplementary Table S3; n = 17; Li et al, 2017) and the FANTOM5 mouse promoterome 4 (Supplementary Table S4; n = 1195; Abugessaisa et al, 2017; Noguchi et al, 2017).…”

Section: Cellular Energy-charge and Atp Turnovermentioning

confidence: 99%

See 1 more Smart Citation

Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP

2019

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Germline mutations in cellular-energy associated genes have been shown to lead to various monogenic disorders. Notably, mitochondrial disorders often impact skeletal muscle, brain, liver, heart, and kidneys, which are the body’s top energy-consuming organs. However, energy-related dysfunctions have not been widely seen as causes of common diseases, although evidence points to such a link for certain disorders. During acute energy consumption, like extreme exercise, cells increase the favorability of the adenylate kinase reaction 2-ADP -> ATP+AMP by AMP deaminase degrading AMP to IMP, which further degrades to inosine and then to purines hypoxanthine -> xanthine -> urate. Thus, increased blood urate levels may act as a barometer of extreme energy consumption. AMP deaminase deficient subjects experience some negative effects like decreased muscle power output, but also positive effects such as decreased diabetes and improved prognosis for chronic heart failure patients. That may reflect decreased energy consumption from maintaining the pool of IMP for salvage to AMP and then ATP, since de novo IMP synthesis requires burning seven ATPs. Similarly, beneficial effects have been seen in heart, skeletal muscle, or brain after treatment with allopurinol or febuxostat to inhibit xanthine oxidoreductase, which catalyzes hypoxanthine -> xanthine and xanthine -> urate reactions. Some disorders of those organs may reflect dysfunction in energy-consumption/production, and the observed beneficial effects related to reinforcement of ATP re-synthesis due to increased hypoxanthine levels in the blood and tissues. Recent clinical studies indicated that treatment with xanthine oxidoreductase inhibitors plus inosine had the strongest impact for increasing the pool of salvageable purines and leading to increased ATP levels in humans, thereby suggesting that this combination is more beneficial than a xanthine oxidoreductase inhibitor alone to treat disorders with ATP deficiency.

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“…[ 26 ] Along with that, the existence of individuals homozygous for genetic xanthine oxidoreductase (XOR) deficiency challenges that hypothesis, since such patients have serum UA levels that are inherently zero but display a complete absence of central nervous symptoms. In fact, XOR is absent or only lowly expressed in the brain, [ 27 – 29 ] the blood brain barrier is minimally permeable to UA, and the concentration of UA in CSF is less than 1/10 of that in the plasma. [ 30 ] Therefore, it is unlikely that such low concentrations of UA have major effects on the management of ROS in neuronal cells.…”

Section: Introductionmentioning

confidence: 99%