Alpha 2-macroglobulin protects some of the protein constituents of dialysis-associated amyloidosis from protease degradation.
A crucial point to know in the prevention and treatment of beta 2-microglobulin (beta 2-m) amyloidosis is the putative resorption of amyloid fibrils in vivo. Although still controversial, long term clinical studies suggest that there is no resorption of amyloid fibrils in vivo, even after the suppression of the primary cause of amyloidosis. Two in vitro studies on murine and human AA amyloidosis as well as Alzheimer's disease suggest that protein constituents of amyloid fibrils may be resorbed. Protein resorption can be inhibited by the antiprotease amyloid P component. We extended these in vitro studies on beta 2-m amyloidosis, and assessed the effect of alpha 2-macroglobulin (alpha 2-M), a serum antiprotease previously found in this type of amyloidosis, on the putative protease induced protein resorption. Here, we show that amyloid proteins, beta 2-m and light chains of immunoglobulins, were degraded by trypsin. Preincubation of the amyloid proteins with alpha 2-M significantly inhibited the trypsin induced protein degradation of lambda chains. These data add further support to the hypothesis proposing a role for alpha 2-M and other antiproteases in the formation and/or persistence of beta 2-m amyloidosis.
Gouin-Charnet
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CNRS, UPR 9008 Centre de Recherches de Biochimie Macromoléculaire, Montpellier, France.
Mourad
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Argilés
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D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism*; D001667:Binding, Competitive; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism*; D066298:In Vitro Techniques; D006435:Renal Dialysis / Q000009:adverse effects; D014357:Trypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000494:pharmacology*; D001613:beta 2-Microglobulin / Q000378:metabolism*
D000682:Amyloid; D007146:Immunoglobulin lambda-Chains; D000511:alpha-Macroglobulins; D001613:beta 2-Microglobulin; D014357:Trypsin