Chemical Biology of 1,2-Naphthoquinone, a Novel Air Pollutant, that Affects Signal Transduction Pathways

Abstract

Prolonged exposure of humans to ambient particulate matter such as diesel exhaust particles (DEP) induces a variety of adverse health effects including cardiovascular diseases, asthma and cancer. Polycyclic aromatic hydrocarbons (PAHs) and their derivatives in DEP are thought to be potential candidates for the deleterious effects of DEP. We have identified 1,2-naphthoquinone (1,2-NQ) as a novel PAH quinone that contaminates DEP. Because 1,2-NQ is covalently bound to macromolecules through reactive thiols (thiolate ions), our rationale was that cellular proteins modified by 1,2-NQ seem to act as a redox-sensor and thus the interaction of thiol proteins with 1,2-NQ may disrupt their functions. To address our hypothesis, we prepared specific antibody against 1,2-NQ bound to proteins. In this review, we introduce an inhibitor of kappaB kinasebeta (IKKbeta) and protein tyrosine phosphatase 1B (PTP1B) as target molecules for 1,2-NQ. Although IKKbeta activates transcription factor NF-kappaB and PTP1B negatively regulates the receptor-protein tyrosine kinase, such as epidermal growth factor receptor (EGFR) in cells, covalent modification of these proteins caused by 1,2-NQ results in inhibition of NF-kappaB activity and transactivation of EGFR.