Academic Journal
Angiotensin-(1-7)-Angiotensin-Converting Enzyme 2 Attenuates Reactive Oxygen Species Formation to Angiotensin II Within the Cell Nucleus
| العنوان: | Angiotensin-(1-7)-Angiotensin-Converting Enzyme 2 Attenuates Reactive Oxygen Species Formation to Angiotensin II Within the Cell Nucleus |
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| المؤلفون: | Gwathmey, TanYa M., Pendergrass, Karl D., Reid, Sean D., Rose, James C., Diz, Debra I., Chappell, Mark C. |
| المصدر: | Hypertension ; volume 55, issue 1, page 166-171 ; ISSN 0194-911X 1524-4563 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: | 2010 |
| الوصف: | The angiotensin (Ang) type 1 receptor (AT 1 R) is highly expressed on renal nuclei and stimulates reactive oxygen species (ROS). It is not known whether other functional components of the Ang system regulate the nuclear Ang II-AT 1 R ROS pathway. Therefore, we examined the expression of Ang receptors in nuclei isolated from the kidneys of young adult (1.5 years) and older adult (3.0 to 5.0 years) sheep. Binding studies in renal nuclei revealed the AT 2 R as the predominant receptor subtype (≈80%) in young sheep, with the Ang-(1-7) (AT 7 R; Mas protein) and AT 1 R antagonists competing for the remaining sites. Conversely, in older sheep, the AT 1 R accounted for ≈85% of nuclear sites, whereas the Ang type 2 receptor and AT 7 R subtypes comprise ≈20% of remaining sites. Ang II increased nuclear ROS to a greater extent in older (97±22%; n=6) versus young animals (7±2%; P =0.01; n=4), and this was abolished by an AT 1 R antagonist. The AT 7 R antagonist D-Ala 7 -Ang-(1-7) increased ROS formation to Ang II by ≈2-fold (174±5% versus 97±22%; P <0.05) in older adults. Immunoblots of renal nuclei revealed protein bands for the AT 7 R and Ang-converting enzyme 2 (ACE2), which metabolizes Ang II to Ang-(1-7). The ACE2 inhibitor MLN4760 also exacerbated the Ang II-dependent formation of ROS (156±15%) and abolished the generation of Ang-(1-7) from Ang II. We conclude that an ACE2-Ang-(1-7)-AT 7 R pathway modulates Ang II-dependent ROS formation within the nucleus, providing a unique protective mechanism against oxidative stress and cell damage. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1161/hypertensionaha.109.141622 |
| DOI: | 10.1161/HYPERTENSIONAHA.109.141622 |
| الاتاحة: | http://dx.doi.org/10.1161/hypertensionaha.109.141622 https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.109.141622 |
| رقم الانضمام: | edsbas.5DEAC1E9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/hypertensionaha.109.141622 |
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