التفاصيل البيبلوغرافية
| العنوان: |
Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons |
| المؤلفون: |
Han-A Park, Nelli Mnatsakanyan, Katheryn Broman, Abigail U. Davis, Jordan May, Pawel Licznerski, Kristi M. Crowe-White, Kimberly H. Lackey, Elizabeth A. Jonas |
| المصدر: |
International Journal of Molecular Sciences; Volume 21; Issue 1; Pages: 220 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2019 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
Bcl-xL, ∆N-Bcl-xL, antioxidant, mitochondria, tocotrienol |
| جغرافية الموضوع: |
agris |
| الوصف: |
B-cell lymphoma-extra large (Bcl-xL) is an anti-apoptotic member of the Bcl2 family of proteins, which supports neurite outgrowth and neurotransmission by improving mitochondrial function. During excitotoxic stimulation, however, Bcl-xL undergoes post-translational cleavage to ∆N-Bcl-xL, and accumulation of ∆N-Bcl-xL causes mitochondrial dysfunction and neuronal death. In this study, we hypothesized that the generation of reactive oxygen species (ROS) during excitotoxicity leads to formation of ∆N-Bcl-xL. We further proposed that the application of an antioxidant with neuroprotective properties such as α-tocotrienol (TCT) will prevent ∆N-Bcl-xL-induced mitochondrial dysfunction via its antioxidant properties. Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both. Glutamate challenge significantly increased cytosolic and mitochondrial ROS and ∆N-Bcl-xL levels. ∆N-Bcl-xL accumulation was accompanied by intracellular ATP depletion, loss of mitochondrial membrane potential, and cell death. α-TCT prevented loss of mitochondrial membrane potential in hippocampal neurons overexpressing ∆N-Bcl-xL, suggesting that ∆N-Bcl-xL caused the loss of mitochondrial function under excitotoxic conditions. Our data suggest that production of ROS is an important cause of ∆N-Bcl-xL formation and that preventing ROS production may be an effective strategy to prevent ∆N-Bcl-xL-mediated mitochondrial dysfunction and thus promote neuronal survival. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Biochemistry; https://dx.doi.org/10.3390/ijms21010220Test |
| DOI: |
10.3390/ijms21010220 |
| الإتاحة: |
https://doi.org/10.3390/ijms21010220Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.5EB3D934 |
| قاعدة البيانات: |
BASE |
