1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea

Kikuno, Shota; Taguchi, Keiko; Iwamoto, Noriko; Yamano, Shigeru; Cho, Arthur K.; Froines, John R.; Kumagai, Yoshito

doi:10.1016/j.taap.2005.06.015

Cited by 49 publications

(40 citation statements)

References 31 publications

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“…We reported recently that 1,2-NQ induces potent contraction of guinea pig tracheal rings ex vivo through transactivation of receptor tyrosine kinases, including EGFR (19). In the present study, exposure of A431 cells to 1,2-NQ resulted in a phosphorylation of EGFR coupled to decreased PTP activity in a concentration-dependent manner.…”

Section: Discussionsupporting

confidence: 58%

“…In earlier studies we observed guinea pig tracheal contraction caused by 1,2-NQ by EGFR phosphorylation, whereas trans-1,2-dihydroxy-1,2-dihydronaphthalene and naphthalene (see Fig. 4A) were without effect on the contractile action and activation of EGFR (19). This suggests an obligatory role of an electrophilic function in the contraction of guinea pig trachea.…”

mentioning

confidence: 65%

“…We recently reported that 1,2-NQ elicits a contraction of smooth muscle in guinea pig tracheal preparations under conditions that indicated transactivation of EGFR was involved in the contraction process (19). These studies also suggested that 1,2-NQ-induced EGFR activation was caused, at least partially, by covalent modification and/or thiol oxidation of PTP1B, leading to the reduction of its dephosphorylation activity.…”

mentioning

confidence: 94%

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Chemical Knockdown of Protein-tyrosine Phosphatase 1B by 1,2-Naphthoquinone through Covalent Modification Causes Persistent Transactivation of Epidermal Growth Factor Receptor

Iwamoto

Sumi

Ishii

et al. 2007

Journal of Biological Chemistry

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118

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1,2-Naphthoquinone (1,2-NQ), an atmospheric contaminant, causes the contraction of guinea pig trachea through the activation of epidermal growth factor receptor (EGFR) by inhibiting protein-tyrosine phosphatases (PTPs). Phosphorylation of EGFR is negatively regulated by PTPs, but details of the mechanism by which 1,2-NQ inhibits PTPs have not been elucidated. Results described in this report demonstrate that 1,2-NQ forms covalent bonds with PTP1B after exposure to human epithelial A431 cells. In this study, a concentration-dependent phosphorylation of EGFR was found to be coupled to the reduction of PTP activity in the cells. The reduction in PTP activity was due to the irreversible modification of PTP1B, and when PTP1B was overexpressed by the cells, the 1,2-NQ-mediated EGFR phosphorylation was suppressed. Studies with purified PTP1B and 1,2-NQ showed that the reduction in enzyme activity was due to a nucleophilic attack by the quinone on the enzyme, to form covalent bonds. Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry analysis and mutation experiments revealed that PTP1B inactivation was primarily due to covalent attachment of the quinone to Cys-121 of the enzyme, with binding to His-25 and Cys-215 as well. Collectively, the results show that covalent attachment of 1,2-NQ to PTP1B is at least partially responsible for the reduction of PTP activity, which leads to prolonged transactivation of EGFR in the cells.

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Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 65%

mentioning

confidence: 94%

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Chemical Knockdown of Protein-tyrosine Phosphatase 1B by 1,2-Naphthoquinone through Covalent Modification Causes Persistent Transactivation of Epidermal Growth Factor Receptor

Iwamoto

Sumi

Ishii

et al. 2007

Journal of Biological Chemistry

Self Cite

118

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“…With 1,2-NQ as a model PAHQ, we found that 1,2-NQ activates a phospholipase A2/lipoxygenase/vaniloid receptor signaling pathway, resulting in increased intracellular calcium content in the smooth muscle cells associated with a contraction of guinea pig tracha. 20) Interestingly, tracheal contraction of guinea pig caused by 1,2-NQ was significantly blocked by pretreatment with either genistein (protein tyrosine kinase inhibitor) or PD153035 [epidermal growth factor receptor (EGFR) inhibitor], 20) suggesting a tracheal contraction coupled to EGFR activation during exposure to 1,2-NQ. As asthma is of one of the major adverse health effects of airborne particulate matter, trachea contraction caused by 1,2-NQ through EGFR phosphorylation is of relevance in the general toxicology of airborne particulate matter.…”

Section: Disruption Of Signal Transduction Through Covalent Modificationmentioning

confidence: 99%

Polycyclic Aromatic Hydrocarbon Quinones as Redox and Electrophilic Chemicals Contaminated in the Atmosphere

Kumagai

2009

JOURNAL OF HEALTH SCIENCE

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Polycyclic aromatic hydrocarbon quinones (PAHQs) produced by combustion of gasoline exhibit two chemical characteristics; one is their electron transfer abilitiy, transferring electrons from reducing agents to molecular oxygen to generate reactive oxygen species (ROS) associated with oxidative stress and the other is their ability to arylate cellular proteins, resulting in the disruption of signal transduction pathways. This review summarizes toxicological and pharmacological significances of such envirnmental chemicals through redox cycling and covalent modification.

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“…In a study of the exposure of bovine aortic endothelial cells to 1,2-NQ, a 32) We have also examined 1,2-NQ effects on the guinea pig tracheal ring preparation and found that it induces a dose-dependent contraction. 33) The underlying mechanism for the contraction was found to be associated with the activation of epidermal growth factor receptor (EGFR) and vanilloid receptor (VR1) signaling. Thus pretreatment with an EGFR inhibitor, PD153035, restored 1,2-NQinduced tracheal contraction, indicating that contraction was, at least in part, attributable to EGFR phosphorylation that activates VR1, resulting in increased intracellular calcium content in the smooth muscle cells.…”

Section: 2-nq An Atmospheric Contaminantmentioning

confidence: 99%

Biological Effects of and Responses to Exposure to Electrophilic Environmental Chemicals

Sumi

2008

JOURNAL OF HEALTH SCIENCE

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Electrophiles readily bind to nucleophilic centers on intracellular macromolecules such as DNA and proteins. Electrophilic attack on DNA results in the formation of an adduct, leading to depurination due to hydrolysis of a purine base such as adenine or guanine. On the other hand, electrophiles also attack proteins, with the thiolate function as the most attractive site. Many protein cysteine (Cys) thiols are affected by their proximity to basic amino acids, which results a decrease in the thiol pKa value. This paper discusses the role of electrophilenucleophile interactions in the adverse health effects of electrophilic environmental chemicals such as arsenic compounds (groundwater contaminant), methylmercury (MeHg; a fish contaminant), and 1,2-naphthoquinone (1,2-NQ; an atmospheric contaminant).

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1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea

Cited by 49 publications

References 31 publications

Chemical Knockdown of Protein-tyrosine Phosphatase 1B by 1,2-Naphthoquinone through Covalent Modification Causes Persistent Transactivation of Epidermal Growth Factor Receptor

Chemical Knockdown of Protein-tyrosine Phosphatase 1B by 1,2-Naphthoquinone through Covalent Modification Causes Persistent Transactivation of Epidermal Growth Factor Receptor

Polycyclic Aromatic Hydrocarbon Quinones as Redox and Electrophilic Chemicals Contaminated in the Atmosphere

Biological Effects of and Responses to Exposure to Electrophilic Environmental Chemicals

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