Figure 2.

Cellular mechanisms by which homocysteine pro-motes cell injury. Homocysteine causes activation of necrosis factor-κB (NF-κB) and enhances production of cytokines (IL-1β, IL-6, and IL-8) resulting in inflammatory reactions, increases intracellular levels of superoxide anion causing oxidative stress, and induces endoplasmic reticulum (ER) stress by causing misfolding of proteins traversing the ER. Homocysteinyl-tRNA increases production of highly reactive derivative homocys-teine thiolactone which damages enzymes and DNA. IRE1, type 1 ER transmembrane protein kinase; ATF6, the activating tran-scription factor 6; PERK, the PKR like ER kinase; SREBP, sterol regulatory element binding protein, PON, paraoxonase.