The H2O2-Generating Enzyme, Xanthine Oxidase, Decreases Luminal Ca2+ Content of the IP3-Sensitive Ca2+ Store in Vascular Endothelial Cells

Authors

  • DONALD E. WESSON,

    1. Departments of Pediatrics, Molecular Physiology & Biophysics, and Medicine, Baylor College of Medicine, Houston, Texas, USA
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  • Dr. STEPHEN J. ELLIOTT

    Corresponding author
    1. Departments of Pediatrics, Molecular Physiology & Biophysics, and Medicine, Baylor College of Medicine, Houston, Texas, USA
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Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, Wisconsin, 53226, USA

ABSTRACT

Objective: Xanthine oxidase inhibits agonist-stimulated Ca2+ signaling in calf pulmonary artery endothelial cells by an H2O2-dependent mechanism. We investigated the effect of xanthine oxidase on luminal Ca2+ content of the inositol-1,4,5-trisphosphate (IP3)-sensitive Ca2+ store.

Methods: Luminal Ca2+ content was estimated from the net release of Ca2+ activated by 2,5-di-t-butylhydroquinone (BHQ), an inhibitor of microsomal Ca2+ pumps.

Results: Initially, xanthine oxidase depleted the IP3-sensitive Ca2+ store of releasable Ca2+, but with more prolonged incubation, the enzyme also depleted non-IP3-sensitive stores. In addition, xanthine oxidase inhibited capacitative Ca2+ influx. Similar results were observed when thapsigargin was substituted for BHQ.

Conclusions: Depletion of luminal Ca2+ content within the IP3-sensitive Ca2+ store contributes to xanthine oxidase inhibition of Ca2+ signaling in vascular endothelial cells.

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