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<p>Protein proclivity to aggregation leads to the formation of insoluble aggregates which slowly build up over the years within blood and different tissues. In humans, the content of these detergent resistant aggregates has been found increased in elder subjects compared to younger ones. The aggregation process is driven not solely by the presence of prone to aggregation proteins but by pro-aggregating agents such as Cu(II) which promotes the aggregation of IgG among others. Cu(II) and Zn(II) induce IgG reversible aggregates. However, co-incubation of Cu(II) with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) renders the aggregate irreversibly insoluble upon metal removal which also becomes detergent resistant. Conversely, in the case of Zn(II)-induced aggregates, the addition of H<sub>2</sub>O<sub>2</sub> in concentrations as high as 3 mM does not yield a detergent resistant aggregate. Contrarily to Cu(II), Zn(II) is redox inactive and unable to react with H<sub>2</sub>O<sub>2</sub>. Notably, the incubation of IgG with Cu(II) and low concentrations of H<sub>2</sub>O<sub>2</sub> (50 µM) leads to the formation of soluble aggregates which can be detected by SDS-PAGE. Boiling allows partial dis-aggregation of the SDS-resistant aggregates and the migration pattern of boiled IgG oxidized in vitro by Cu(II)/H<sub>2</sub>O<sub>2</sub> is similar to that observed in the aggregates from human sera. The presence of IgG was confirmed by western blot in SDS-resistant aggregates found in elder and young sera. Therefore, we speculate that Cu(II) reaction with H<sub>2</sub>O<sub>2</sub> may contribute to IgG-enriched circulating protein aggregates and their clinical relevance should be further explored as they could resemble circulating immune-complexes which possess several pro-inflammatory features.</p>

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Oxidative environments promote the formation of detergent-resistant IgG aggregates mediated by Cu(II) assessed by optical density: implications in vivo

  • 期刊论文

  • 发表日期：

    2025年11月13日

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  • Christian Saporito-Magriña,
  • Lila Lopez-Montañana,
  • María Laura Facio,
  • Guadalupe Pagano,
  • Aldana Rodriguez,
  • Juan Ignacio Bellida,
  • Marisa Gabriela Repetto

摘要

Protein proclivity to aggregation leads to the formation of insoluble aggregates which slowly build up over the years within blood and different tissues. In humans, the content of these detergent resistant aggregates has been found increased in elder subjects compared to younger ones. The aggregation process is driven not solely by the presence of prone to aggregation proteins but by pro-aggregating agents such as Cu(II) which promotes the aggregation of IgG among others. Cu(II) and Zn(II) induce IgG reversible aggregates. However, co-incubation of Cu(II) with hydrogen peroxide (H2O2) renders the aggregate irreversibly insoluble upon metal removal which also becomes detergent resistant. Conversely, in the case of Zn(II)-induced aggregates, the addition of H2O2 in concentrations as high as 3 mM does not yield a detergent resistant aggregate. Contrarily to Cu(II), Zn(II) is redox inactive and unable to react with H2O2. Notably, the incubation of IgG with Cu(II) and low concentrations of H2O2 (50 µM) leads to the formation of soluble aggregates which can be detected by SDS-PAGE. Boiling allows partial dis-aggregation of the SDS-resistant aggregates and the migration pattern of boiled IgG oxidized in vitro by Cu(II)/H2O2 is similar to that observed in the aggregates from human sera. The presence of IgG was confirmed by western blot in SDS-resistant aggregates found in elder and young sera. Therefore, we speculate that Cu(II) reaction with H2O2 may contribute to IgG-enriched circulating protein aggregates and their clinical relevance should be further explored as they could resemble circulating immune-complexes which possess several pro-inflammatory features.