We have located links that may give you full text access.
Nrf2-mediated neuroprotection against oxygen-glucose deprivation/reperfusion injury by emodin via AMPK-dependent inhibition of GSK-3β.
Journal of Pharmacy and Pharmacology 2018 April
OBJECTIVES: Our study verified the neuroprotective properties of emodin against oxygen-glucose deprivation/reoxygenation (OGD/R) and demonstrated its mechanism.
METHODS: Human neuronal SH-SY5Y cells were investigated by analysing cell viability, lactate dehydrogenase levels, expression of molecules related to apoptotic cell death, and using biochemical techniques, flow cytometry and Western blot assays.
KEY FINDINGS: Emodin reduced OGD/R-lead to neurotoxicity in SH-SY5Y cells. OGD/R significantly increased levels of cleaved poly ADP ribose polymerase, cleaved caspase-3, cleaved caspase-9, p53, p21 and Bax protein. However, emodin treatment effectively inhibited these OGD/R-induced changes. Emodin treatment also increased HO-1 and NQO1 expression in a concentration- and time-dependent manner and caused antioxidant response element (ARE) transcription activity and nuclear Nrf2 accumulation. Emodin phosphorylated AMPK and GSK3β, and pretreatment of cells with an AMPK inhibitor suppressed emodin-induced nuclear Nrf2 accumulation and HO-1 and NQO1 expression. AMPK inhibitor treatment decreased GSK3β phosphorylation, suggesting that AMPK is upstream of GSK3β, Nrf2, HO-1 and NQO1. Emodin's neuroprotective effect was completely blocked by HO-1, NQO1 and Nrf2 knock-down and an AMPK inhibitor, indicating the action of AMPK/GSK3β/Nrf2/ARE in the neuroprotective effect of emodin subjected to OGD/R.
CONCLUSIONS: Emodin treatment protected against OGD/R-lead to neurotoxicity by potentiating Nrf2/ARE-regulated neuroprotection through the AMPK/GSK3β pathway, indicating that emodin may be useful for treating neurodegenerative disorders.
METHODS: Human neuronal SH-SY5Y cells were investigated by analysing cell viability, lactate dehydrogenase levels, expression of molecules related to apoptotic cell death, and using biochemical techniques, flow cytometry and Western blot assays.
KEY FINDINGS: Emodin reduced OGD/R-lead to neurotoxicity in SH-SY5Y cells. OGD/R significantly increased levels of cleaved poly ADP ribose polymerase, cleaved caspase-3, cleaved caspase-9, p53, p21 and Bax protein. However, emodin treatment effectively inhibited these OGD/R-induced changes. Emodin treatment also increased HO-1 and NQO1 expression in a concentration- and time-dependent manner and caused antioxidant response element (ARE) transcription activity and nuclear Nrf2 accumulation. Emodin phosphorylated AMPK and GSK3β, and pretreatment of cells with an AMPK inhibitor suppressed emodin-induced nuclear Nrf2 accumulation and HO-1 and NQO1 expression. AMPK inhibitor treatment decreased GSK3β phosphorylation, suggesting that AMPK is upstream of GSK3β, Nrf2, HO-1 and NQO1. Emodin's neuroprotective effect was completely blocked by HO-1, NQO1 and Nrf2 knock-down and an AMPK inhibitor, indicating the action of AMPK/GSK3β/Nrf2/ARE in the neuroprotective effect of emodin subjected to OGD/R.
CONCLUSIONS: Emodin treatment protected against OGD/R-lead to neurotoxicity by potentiating Nrf2/ARE-regulated neuroprotection through the AMPK/GSK3β pathway, indicating that emodin may be useful for treating neurodegenerative disorders.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.Circulation 2024 April 19
Essential thrombocythaemia: A contemporary approach with new drugs on the horizon.British Journal of Haematology 2024 April 9
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app