Involvement of intracellular Ca2+ in oxidant‐induced NF‐κB activation

[摘要]

In human Jurkat T cells and its subclone Wurzburg cells oxidant challenge elevated [Ca²⁺]i by mobilizing Ca²⁺ from intracellular stores. In Jurkat cells this effect was rapid and transient, but in Wurzburg cells the response was slow and sustained. H₂0₂-induced NF-κB activation in Wurzburg cells was not influenced by the presence of extracellular EGTA but was totally inhibited in cells that were loaded with esterified EGTA. In Jurkat cells that are not sensitive to H₂0₂-induced NF-κB activation, H₂0₂ potentiated NF-κB activation in the presence of sustained high [Ca²⁺]i following thapsigargin treatment. NF-κB regulatory effect of α-lipoate and N-acetylcysteine appeared to be, at least in part, due to their ability to stabilize elevation of [Ca²⁺]i following oxidant challenge. Results of this study indicate that a sustained elevated [Ca²⁺]i is a significant factor in oxidant-induced NF-κB activation.

[学科分类] 生物化学/生物物理

[关键词] Antioxidant;Redox;Transcription;NF-κB;Calcium;Thiol;NF-κB;nuclear factor κB;IL-2;interleukin-2;ROS;reactive oxygen species;[Ca2+i;intracellular Ca2+ concentration;indo-1;1-[2-amino-5-{6-carboxylindol-2-yl}-phenoxy]-2-{2′-amino-5′-methylphenoxy}ethane N;N;N′;N′-tetraacetic acid;EMSA;electrophoretic mobility shift assay;DTT;dithiothreitol;FCS;fetal calf serum;FACS;fluorescence-activated cell sorter;EGTA;ethyleneglycoltetraacetic acid;EDTA;ethylenediaminetetraacetic acid;NAC;N-acetyl-l-cysteine;TMB-8;8-(diethylamino)octyl-3;4;5-trimethoxybenzoate;EGTA-AM;acetomethoxyl ester of ethyleneglycoltetraacetic acid