Redox cycling of 9,10-phenanthrenequinone activates epidermal growth factor receptor signaling through <i>S</i>-oxidation of protein tyrosine phosphatase 1B

• DOI: 10.2131/jts.45.349
• Publication Date: 2020-06-03T22:05:44Z
• Authors: Nho Cong Luong; Yumi Abiko; Takahiro Shibata; Koji Uchida; Eiji Warabi; Midori Suzuki; Takuya Noguchi; Atsushi Matsuzawa; Yoshito Kumagai
• Keywords: A431 cells; Pro-oxidant

9,10-Phenanthrenequinone (9,10-PQ) is a polycyclic aromatic hydrocarbon quinone contaminated in diesel exhaust particles and particulate matter 2.5. It an efficient electron acceptor that induces redox cycling with donors, resulting excessive reactive oxygen species oxidized protein production cells. The current study examined whether 9,10-PQ could activate epidermal growth factor receptor (EGFR) signaling A431 cells through S-oxidation of its negative regulators such as tyrosine phosphatase (PTP) 1B. recombinant human PTP1B at Cys215 inhibited catalytic activity, effect was blocked by catalase (CAT), whereas cis-9,10-dihydroxy-9,10-dihydrophenanthrene (DDP), which lacks had no on activity. Exposure to 9,10-PQ, but not DDP, activated EGFR downstream extracellular signal-regulated kinase 1/2 (ERK1/2), coupled decrease cellular PTP Immunoprecipitation UPLC-MSE revealed easily undergoes oxidation during exposure 9,10-PQ. Pretreatment polyethylene glycol conjugated CAT (PEG-CAT) abolished 9,10-PQ-generated H2O2 significantly the activation EGFR-ERK1/2 indicating involvement because scavenging agents for hydroxyl radicals signal activation. These results suggest air pollutant producing H2O2, activates signaling, presumably PTPs PTP1B, cascade may contribute, least part, responses