Abstract
Dexmedetomidine, a potent α2-adrenoceptor (α2-AR) agonist, is extensively used in the operating room (OR) and intensive care unit (ICU) and has been applied for the treatment of several diseases. Western blotting has been routinely used to investigate the protein levels of α-adrenergic receptor (α-AR), 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) in neurons. The CCK-8 assay was used to determine cell survival rates while the Co-IP assay was used to investigate the binding ability between α2-AR and Nrf2. The TUNEL assay was used to detect cell apoptosis in neurons. 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 the increased protein expression of α2-AR in OGD/R-treated neurons and enhanced survival rate of OGD/R-treated neurons. From a mechanistic point-of-view, Nrf2 can effectively bind with α2-AR. Silencing Nrf2 reversed the effects of dexmedetomidine on cell viability, oxidative stress, and neuronal apoptosis in OGD/R-treated neurons. 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.
Highlights
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
Collectively, our data indicate that elucidated that the activation of α2-AR by dexmedetomidine had a protective effect in neurons against oxygen and glucose deprivation/reoxygenation (OGD/R)-triggered oxidative stress and neuronal apoptosis by modulating the NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, providing a novel way forward to develop clinical therapies to reduce oxidative stress induced by neuronal injury
We found that dexmedetomidine treatment significantly increased the protein levels of α2-AR, nuclear Nrf2 (n-Nrf2), H0-1, NAD(P)H: quinone oxidoreductase-1 (NQO-1) and superoxide dismutase (SOD) but reduced the protein level of cytoplasm Nrf2 (c-Nrf2) in OGD/R-treated neurons (@P
Summary
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. 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. There has been some progress in the treatment of ischemia and evaluating the progression of patients affected by post-cerebral ischemia. Studies have revealed that a range of mechanisms are involved in post-cerebral ischemia, including oxidative stress, neuronal apoptosis and excitatory toxicity; collectively, these processes can lead to irreversible brain damage [3]. Strategies for reducing neuronal injury have been investigated, at least to some extent, the prognosis of patients affected by this condition is still not satisfactory. It is vital that we investigate the pathological process underlying neuronal injury so that we may identify new treatment strategies for ischemic stroke
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