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Overexpression of lemur tyrosine kinase-2 protects neurons from oxygen-glucose deprivation/reoxygenation-induced injury through reinforcement of Nrf2 signaling by modulating GSK-3β phosphorylation.
Biochem Biophys Res Commun. 2020 01 22; 521(4):964-970.BB

Abstract

Lemur tyrosine kinase-2 (LMTK2), a newly identified serine/threonine kinase, is a potential regulator of cell survival and apoptosis. However, little is known about its role in regulating neuronal survival during cerebral ischemia/reperfusion injury. The present study aimed to explore the potential function of LMTK2 in regulating neuronal survival using an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury. Herein, we found that LMTK2 expression was markedly decreased in neurons following OGD/R exposure. Gain-of-function experiments demonstrated that LMTK2 overexpression significantly improved the viability and reduced apoptosis of neurons with OGD/R-induced injury. Moreover, LMTK2 overexpression reduced the production of reactive oxygen species (ROS) in OGD/R-exposed neurons. Notably, our results elucidated that LMTK2 overexpression reinforced the activation of nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response element (ARE) antioxidant signaling associated with increased glycogen synthase kinase-3β (GSK-3β) phosphorylation. GSK-3β inhibition by its specific inhibitor significantly reversed LMTK2-inhibition-linked apoptosis and ROS production. Additionally, silencing Nrf2 partially reversed the LMTK2-overexpression-mediated neuroprotective effect in OGD/R-injured neurons. Taken together, our results demonstrated that LMTK2 overexpression alleviated OGD/R-induced neuronal apoptosis and oxidative damage by enhancing Nrf2/ARE antioxidant signaling via modulation of GSK-3β phosphorylation. Our study suggests LMTK2 is a potential target for neuroprotection during cerebral ischemia/reperfusion.

Authors+Show Affiliations

Department of Anesthesiology, The Hospital of Xidian Group, Xi'an, Shaanxi, 710077, China.Department of Anesthesiology, The Hospital of Xidian Group, Xi'an, Shaanxi, 710077, China. Electronic address: gaominxd@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31722791

Citation

Bao, Hong, and Min Gao. "Overexpression of Lemur Tyrosine Kinase-2 Protects Neurons From Oxygen-glucose Deprivation/reoxygenation-induced Injury Through Reinforcement of Nrf2 Signaling By Modulating GSK-3β Phosphorylation." Biochemical and Biophysical Research Communications, vol. 521, no. 4, 2020, pp. 964-970.
Bao H, Gao M. Overexpression of lemur tyrosine kinase-2 protects neurons from oxygen-glucose deprivation/reoxygenation-induced injury through reinforcement of Nrf2 signaling by modulating GSK-3β phosphorylation. Biochem Biophys Res Commun. 2020;521(4):964-970.
Bao, H., & Gao, M. (2020). Overexpression of lemur tyrosine kinase-2 protects neurons from oxygen-glucose deprivation/reoxygenation-induced injury through reinforcement of Nrf2 signaling by modulating GSK-3β phosphorylation. Biochemical and Biophysical Research Communications, 521(4), 964-970. https://doi.org/10.1016/j.bbrc.2019.11.002
Bao H, Gao M. Overexpression of Lemur Tyrosine Kinase-2 Protects Neurons From Oxygen-glucose Deprivation/reoxygenation-induced Injury Through Reinforcement of Nrf2 Signaling By Modulating GSK-3β Phosphorylation. Biochem Biophys Res Commun. 2020 01 22;521(4):964-970. PubMed PMID: 31722791.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of lemur tyrosine kinase-2 protects neurons from oxygen-glucose deprivation/reoxygenation-induced injury through reinforcement of Nrf2 signaling by modulating GSK-3β phosphorylation. AU - Bao,Hong, AU - Gao,Min, Y1 - 2019/11/10/ PY - 2019/10/24/received PY - 2019/11/01/accepted PY - 2019/11/15/pubmed PY - 2020/7/28/medline PY - 2019/11/15/entrez KW - Cerebral ischemia/reperfusion injury KW - GSK-3β KW - LMTK2 KW - Nrf2 KW - OGD/R SP - 964 EP - 970 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 521 IS - 4 N2 - Lemur tyrosine kinase-2 (LMTK2), a newly identified serine/threonine kinase, is a potential regulator of cell survival and apoptosis. However, little is known about its role in regulating neuronal survival during cerebral ischemia/reperfusion injury. The present study aimed to explore the potential function of LMTK2 in regulating neuronal survival using an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury. Herein, we found that LMTK2 expression was markedly decreased in neurons following OGD/R exposure. Gain-of-function experiments demonstrated that LMTK2 overexpression significantly improved the viability and reduced apoptosis of neurons with OGD/R-induced injury. Moreover, LMTK2 overexpression reduced the production of reactive oxygen species (ROS) in OGD/R-exposed neurons. Notably, our results elucidated that LMTK2 overexpression reinforced the activation of nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response element (ARE) antioxidant signaling associated with increased glycogen synthase kinase-3β (GSK-3β) phosphorylation. GSK-3β inhibition by its specific inhibitor significantly reversed LMTK2-inhibition-linked apoptosis and ROS production. Additionally, silencing Nrf2 partially reversed the LMTK2-overexpression-mediated neuroprotective effect in OGD/R-injured neurons. Taken together, our results demonstrated that LMTK2 overexpression alleviated OGD/R-induced neuronal apoptosis and oxidative damage by enhancing Nrf2/ARE antioxidant signaling via modulation of GSK-3β phosphorylation. Our study suggests LMTK2 is a potential target for neuroprotection during cerebral ischemia/reperfusion. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/31722791/Overexpression_of_lemur_tyrosine_kinase_2_protects_neurons_from_oxygen_glucose_deprivation/reoxygenation_induced_injury_through_reinforcement_of_Nrf2_signaling_by_modulating_GSK_3β_phosphorylation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(19)32122-9 DB - PRIME DP - Unbound Medicine ER -