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Research article
Deming Xu
The Affiliated Hospital (Group) of Putian University
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Dexmedetomidine, a potent α2-adrenoceptor (α2-AR) agonist, is extensively used in the operating room (OR) and intensive care unit (ICU) and has applied in several diseases. However, the precise role of dexmedetomidine in oxygen and glucose deprivation/reoxygenation (OGD/R)-treated neurons, and the mechanisms underlying its effect, has yet to be elucidated.
Methods: OGD/R-treated neurons served as a cellular model in our study. Western blotting was used to investigate the protein levels of α-adrenergic receptor (α-AR) in OGD/R-treated neurons, apoptosis related proteins (Bcl-2, Bax and Cleaved Caspase 3) and a range of proteins associated with the Nrf2/ARE pathway (Nrf2, HO-1, NQO-1, SOD). The CCK-8 assay was used to determine cell survival rates while Co-IP was used to determine the interactions between α2-AR and Nrf2. The TUNEL assay was used to detect the levels of apoptosis in neurons.
Results: OGD/R treatment reduced the level of α2-AR protein in neurons and reduced neuronal survival in a time-dependent manner. However, treatment with dexmedetomidine led to an elevation of α2-AR protein expression in OGD/R-treated neurons and the survival rate of OGD/R-treated neurons. These results indicated that dexmedetomidine treatment promoted the viability of OGD/R-treated neurons but inhibited OGD/R-mediated oxidative stress and neuronal apoptosis. From a mechanistic point-of-view, Nrf2 can bind effectively with α2-AR. We believe that dexmedetomidine exerted effect on the Nrf2/ARE pathway in OGD/R-treated neurons. Silencing the expression of Nrf2 reversed the effects of dexmedetomidine on cell viability, oxidative stress, and neuronal apoptosis in OGD/R-treated neurons.
Conclusion: Collectively, our data indicate that elucidated that the activation of α2-AR by dexmedetomidine had a protective effect in neurons against OGD/R-triggered oxidative stress and neuronal apoptosis by modulating the Nrf2/ARE pathway, thus providing a novel way forward to develop clinical therapies to reduce oxidative stress induced by neuronal injury.
Keywords
α2-adrenoreceptor, dexmedetomidine, OGD/R-induced oxidative stress, Nrf2/ARE pathway, neurons, neuronal apoptosis
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Deming Xu
The Affiliated Hospital (Group) of Putian University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Published
View the published article at Toxicology Mechanisms and Methods.
Version 1
Posted 22 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Anesthesiology & Pain Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Toxicology Mechanisms and Methods.
Background: Dexmedetomidine, a potent α2-adrenoceptor (α2-AR) agonist, is extensively used in the operating room (OR) and intensive care unit (ICU) and has applied in several diseases. However, the precise role of dexmedetomidine in oxygen and glucose deprivation/reoxygenation (OGD/R)-treated neurons, and the mechanisms underlying its effect, has yet to be elucidated.
Methods: OGD/R-treated neurons served as a cellular model in our study. Western blotting was used to investigate the protein levels of α-adrenergic receptor (α-AR) in OGD/R-treated neurons, apoptosis related proteins (Bcl-2, Bax and Cleaved Caspase 3) and a range of proteins associated with the Nrf2/ARE pathway (Nrf2, HO-1, NQO-1, SOD). The CCK-8 assay was used to determine cell survival rates while Co-IP was used to determine the interactions between α2-AR and Nrf2. The TUNEL assay was used to detect the levels of apoptosis in neurons.
Results: OGD/R treatment reduced the level of α2-AR protein in neurons and reduced neuronal survival in a time-dependent manner. However, treatment with dexmedetomidine led to an elevation of α2-AR protein expression in OGD/R-treated neurons and the survival rate of OGD/R-treated neurons. These results indicated that dexmedetomidine treatment promoted the viability of OGD/R-treated neurons but inhibited OGD/R-mediated oxidative stress and neuronal apoptosis. From a mechanistic point-of-view, Nrf2 can bind effectively with α2-AR. We believe that dexmedetomidine exerted effect on the Nrf2/ARE pathway in OGD/R-treated neurons. Silencing the expression of Nrf2 reversed the effects of dexmedetomidine on cell viability, oxidative stress, and neuronal apoptosis in OGD/R-treated neurons.
Conclusion: Collectively, our data indicate that elucidated that the activation of α2-AR by dexmedetomidine had a protective effect in neurons against OGD/R-triggered oxidative stress and neuronal apoptosis by modulating the Nrf2/ARE pathway, thus providing a novel way forward to develop clinical therapies to reduce oxidative stress induced by neuronal injury.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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