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Advanced glycation end products (AGEs) activate mast cells

Discussion in 'Mast Cell Disorders/Mastocytosis' started by nanonug, Jul 13, 2012.

  1. nanonug

    nanonug Senior Member

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    From "Advanced glycation end products (AGEs) activate mast cells":


    BACKGROUND AND PURPOSE
    Advanced glycation endproducts (AGEs) represent one of the many types of chemical modifications that occur with age in long-lived proteins. AGEs also accumulate in pathologies such as diabetes, cardiovascular diseases, neurodegeneration and cancer. Mast cells are major effectors of acute inflammatory responses that also contribute to the progression of chronic diseases. Here we investigated interactions between AGEs and mast cells.

    EXPERIMENTAL APPROACHES
    Histamine secretion from AGEs-stimulated mast cells was measured. Involvement of a receptor for AGEs, RAGE, was assessed by PCR, immunostaining and use of inhibitors of RAGE. Production of reactive oxygen species (ROS) and cytokines was measured.

    KEY RESULTS
    Advanced glycation endproducts dose-dependently induced mast cell exocytosis with maximal effects being obtained within 20 s. RAGE mRNA was detected and intact cells were immunostained by a specific anti-RAGE monoclonal antibody. AGEs-induced exocytosis was inhibited by an anti-RAGE antibody and by low molecular weight heparin, a known RAGE antagonist. RAGE expression levels were unaltered after 3 h treatment with AGEs. AGE-RAGE signalling in mast cells involves Pertussis toxin-sensitive Gi-proteins and intracellular Ca2+ increases as pretreatment with Pertussis toxin, caffeine, 2-APB and BAPTA-AM inhibited AGE-induced exocytosis. AGEs also rapidly stimulated ROS production. After 6 h treatment with AGEs, the pattern of cytokine secretion was unaltered compared with controls.

    CONCLUSIONS AND IMPLICATIONS
    Advanced glycation endproducts activated mast cells and may contribute to a vicious cycle involving generation of ROS, increased formation of AGEs, activation of RAGE and to the increased low-grade inflammation typical of chronic diseases.
    Waverunner likes this.
  2. Hip

    Hip Senior Member

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    Very interesting.

    Advanced glycation end products (AGEs) are created by cooking foods until the foods brown: AGEs are formed within the browning that appears when frying, baking, grilling, toasting or roasting foods.

    The AGEs in the food browning would be activating mast cells, which in turn will increase inflammation and increase reactive oxygen species in those that eat browned food.

    So this might explain why raw food diets have been reported to put ME/CFS into remission: there are no AGEs in raw food.



    Browning on foods includes the browning of meats when fried, baked, grilled, toasted or roasted, as well as the browning that appears on potatoes, wheat, vegetables, coffee, etc when fried, baked, grilled, toasted or roasted. The caramel coloring found in soft drinks also contains AGEs.

    Yes, that's right: browning, the stuff that makes food taste so nice, is the dietary source of the AGEs.

    The specific type of browning reaction that causes these problematic AGEs to appear in food is Maillard reaction browning.

    The Maillard reaction is chemical reaction between an amino acid and a sugar. The Maillard reaction occurs at cooking temperatures of around 150 ºC to 260 ºC.

    Boiled food usually does not have any significant browning, because the presence of water tends to keep the temperature lower — below the temperature required for the Maillard reaction.

    So perhaps a boiled food diet might also be effective for treating ME/CFS?
    camas likes this.
  3. nanonug

    nanonug Senior Member

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    Very astute observation!

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