Figure 1. Studies on H₂O₂ signaling from the Forman laboratory.

The studies are for the endogenous production of H₂O₂. H₂O₂ produced by Nox2 can activate Src kinases [105] and cause inactivation of PTP1B through glutathionylation [90]. Together the activation of a Src kinase and inactivation of PTP1B cause ERK activation [53]. H₂O₂ produced by Nox2 is also used to oxidize thioredoxin, which allows activation of the ASK1 to JNK pathway. Stimulation of Nox2 also leads to H₂O₂-dependent NF-κB activation [51]. H₂O₂ produced by redox cycling of quinones activates Nrf2 and Phase 2 gene expression [37]. Silica activates Nox2 generation of H₂O₂ that is then used in the Fenton reaction to initiate localized lipid peroxidation that results in lipid raft disruption, activation of PC-PLC, and NF-κB-dependent cytokine production.