Complex interrelationships between nitro-alkene-dependent inhibition of soluble epoxide hydrolase, inflammation and tumor growth
| Autor: | Christopher H. Switzer, Joseph R. Burgoyne, Philip Eaton, Tony Ng, Hyun-Ju Cho, Rebecca L. Charles, Alisa Kamynina, Olena Rudyk |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Epoxide hydrolase 2 Angiogenesis Clinical Biochemistry Inflammation Alkenes Biochemistry 03 medical and health sciences Mice 0302 clinical medicine In vivo Neoplasms Hydrolase medicine Animals lcsh:QH301-705.5 Epoxide Hydrolases lcsh:R5-920 Chemistry Organic Chemistry Lewis lung carcinoma Endothelial Cells Molecular biology In vitro 030104 developmental biology lcsh:Biology (General) cardiovascular system medicine.symptom lcsh:Medicine (General) 030217 neurology & neurosurgery Research Paper |
| Zdroj: | Redox Biology Redox Biology, Vol 29, Iss, Pp-(2020) |
| ISSN: | 2213-2317 |
| Popis: | Nitro-oleate (10-nitro-octadec-9-enoic acid), which inhibits soluble epoxide hydrolase (sEH) by covalently adducting to C521, increases the abundance of epoxyeicosatrienoic acids (EETs) that can be health promoting, for example by lowering blood pressure or their anti-inflammatory actions. However, perhaps consistent with their impact on angiogenesis, increases in EETs may exacerbate progression of some cancers. To assess this, Lewis lung carcinoma (LLc1) cells were exposed to oleate or nitro-oleate, with the latter inhibiting the hydrolase and increasing their proliferation and migration in vitro. The enhanced proliferation induced by nitro-oleate was EET-dependent, being attenuated by the ETT-receptor antagonist 14,15-EE-5(Z)-E. LLc1 cells were engineered to stably overexpress wild-type or C521S sEH, with the latter exhibiting resistance to nitro-oleate-dependent hydrolase inhibition and the associated stimulation of tumor growth in vitro or in vivo. Nitro-oleate also increased migration in endothelial cells isolated from wild-type (WT) mice, but not those from C521S sEH knock-in (KI) transgenic mice genetically modified to render the hydrolase electrophile-resistant. These observations were consistent with nitro-oleate promoting cancer progression, and so the impact of this electrophile was examined in vivo again, but this time comparing growth of LLc1 cells expressing constitutive levels of wild-type hydrolase when implanted into WT or KI mice. Nitro-oleate inhibited tumor sEH (P Graphical abstract Image 1 |
| Databáze: | OpenAIRE |
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