Nitro-Oleic Acid Regulates Endothelin Signaling in Human Endothelial Cells.

نویسندگان

  • Emilia Kansanen
  • Suvi M Kuosmanen
  • Anna-Kaisa Ruotsalainen
  • Heidi Hynynen
  • Anna-Liisa Levonen
چکیده

Nitro-fatty acids are reactive signaling mediators that are formed when unsaturated fatty acids react with nitric oxide or nitric oxide-derived species. Nitro-fatty acids can modify specific signaling pathways via post-translational modifications of Cys residues in key regulatory proteins. One of the signaling cascades activated by nitro-fatty acids is the Keap1-Nrf2 pathway. We have previously studied the effects of nitro-oleic acid (OA-NO2) on the human endothelial cell transcriptome. We observed that endothelin receptor B [ET-B (gene name EDNRB)], the receptor mediating the vasodilatory effects of endothelin-1 (ET-1) is induced by OA-NO2 Inasmuch as ET-1 is one of the key regulators of vascular tone, we chose to examine in more detail the effect of OA-NO2 on endothelin signaling in human endothelial cells. Nrf2 was found to regulate the OA-NO2-induced transcription of ET-B in human and mouse endothelial cells. Furthermore, chromatin immunoprecipitation analysis revealed that OA-NO2 increased the binding of Nrf2 to an antioxidant response element in the enhancer region of the EDNRB gene. In addition, we show that the overexpression of both OA-NO2 and Nrf2 substantially decreased and that Nrf2 silencing increased the ET-1 concentration in the culture media of endothelial cells. The change in the extracellular ET-1 concentration was dependent on ET-B receptor expression. These data suggest that OA-NO2 modulates endothelin signaling by increasing Nrf2-dependent expression of the ET-B receptor in endothelial cells, which in turn mediates the decrease in extracellular ET-1 concentration. Based on these results, we propose that OA-NO2 and Nrf2 may alleviate the vasoconstrictive effects of ET-1 by removing it from the circulation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Nrf2-dependent and -independent responses to nitro-fatty acids in human endothelial cells: identification of heat shock response as the major pathway activated by nitro-oleic acid.

Electrophilic fatty acid derivatives, including nitrolinoleic acid and nitro-oleic acid (OA-NO(2)), can mediate anti-inflammatory and pro-survival signaling reactions. The transcription factor Nrf2, activated by electrophilic fatty acids, suppresses redox-sensitive pro-inflammatory gene expression and protects against vascular endothelial oxidative injury. It was therefore postulated that activ...

متن کامل

Fatty acid transduction of nitric oxide signaling: nitrolinoleic acid potently activates endothelial heme oxygenase 1 expression.

Nitroalkenes are a class of cell signaling mediators generated by NO and fatty acid-dependent redox reactions. Nitrated fatty acids such as 10- and 12-nitro-9,12-octadecadienoic acid (nitrolinoleic acid, LNO(2)) exhibit pluripotent antiinflammatory cell signaling properties. Heme oxygenase 1 (HO-1) is up-regulated as an adaptive response to inflammatory mediators and oxidative stress. LNO(2) (1...

متن کامل

Protection of nitro-fatty acid against kidney diseases.

Nitrated derivatives of unsaturated fatty acids are endogenously formed under oxidative and nitrative stress condition and are defined as electrophilic fatty acids containing a nitro group to a carbon-carbon double bond. Among the most studied nitro derivatives of unsaturated fatty acids are nitro-oleic acid (OA-NO2) and nitro-linoleic acid (LNO2). These products exhibit novel protective action...

متن کامل

Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice.

OBJECTIVE Inflammatory processes and foam cell formation are key determinants in the initiation and progression of atherosclerosis. Electrophilic nitro-fatty acids, byproducts of nitric oxide- and nitrite-dependent redox reactions of unsaturated fatty acids, exhibit antiinflammatory signaling actions in inflammatory and vascular cell model systems. The in vivo action of nitro-fatty acids in chr...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Molecular pharmacology

دوره 92 4  شماره 

صفحات  -

تاریخ انتشار 2017