Intermittent High Glucose Enhances Apoptosis Related to Oxidative Stress in Human Umbilical Vein Endothelial Cells

DOI PDF PDF 被引用文献36件
  • Lisa Quagliaro
    Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy
  • Ludovica Piconi
    Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy
  • Roberta Assaloni
    Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Udine, Italy
  • Lucia Martinelli
    Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Udine, Italy
  • Enrico Motz
    Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Udine, Italy
  • Antonio Ceriello
    Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Udine, Italy

抄録

<jats:p>The effects of intermittent and constant high glucose in the formation of nitrotyrosine and 8-hydroxydeoxyguanosine (markers of oxidative stress), as well as the possible linkage between oxidative stress and apoptosis in endothelial cells, have been evaluated. Stable high glucose increased nitrotyrosine, 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis levels. However, these effects were more pronounced in intermittent high glucose. Protein kinase C (PKC) was elevated in both such conditions, particularly in intermittent glucose. The adding of the PKC inhibitors bisindolylmaleimide-I and LY379196, a specific inhibitor of PKC-β isoforms, normalized nitrotyrosine and reduced 8-OHdG concentration and cell apoptosis in both stable and intermittent high glucose. Similar results were obtained with the MnSOD mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin chloride that normalized nitrotyrosine, 8-OHdG, and apoptosis and inhibited PKC activation. NAD(P)H oxidase was also measured. NAD(P)H oxidase components p47phox, p67phox, and p22phox was overexpressed during both stable and intermittent high glucose. PKC inhibition and MnSOD mimetic normalized this phenomenon. In conclusion, our study shows that the exposure of endothelial cells to both stable and intermittent high glucose stimulates reactive oxygen species overproduction also through PKC-dependent activation of NAD(P)H oxidase, leading to increased cellular apoptosis. Our data suggest that glucose fluctuations may also be involved in the development of vascular injury in diabetes.</jats:p>

収録刊行物

  • Diabetes

    Diabetes 52 (11), 2795-2804, 2003-11-01

    American Diabetes Association

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