학술논문
Peroxisome Proliferator-Activated Receptor y Coactivator 1a Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling
Article
Article
Document Type
Report
Author
Source
International Journal of Molecular Sciences. October 1, 2020, Vol. 21 Issue 19, p1jj, 23 p.
Subject
Language
English
ISSN
1422-0067
Abstract
1. Introduction Epilepsy is one of the most common serious brain conditions characterized by the recurrence of unprovoked seizures, affecting more than 70 million people worldwide [1]. Status epilepticus is [...]
Status epilepticus may cause molecular and cellular events, leading to hippocampal neuronal cell death. Peroxisome proliferator-activated receptor [gamma] coactivator 1-[alpha] (PGC-1[alpha]) is an important regulator of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2), also known as fetal liver kinase receptor 1 (Flk-1). Resveratrol is an activator of PGC-1[alpha]. It has been suggested to provide neuroprotective effects in epilepsy, stroke, and neurodegenerative diseases. In the present study, we used microinjection of kainic acid into the left hippocampal CA3 region in Sprague Dawley rats to induce bilateral prolonged seizure activity. Upregulating the PGC-1[alpha] pathway will increase VEGF/VEGFR2 (Flk-1) signaling and further activate some survival signaling that includes the mitogen activated protein kinase kinase (MEK)/mitogen activated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways and offer neuroprotectionasaconsequence of apoptosis in the hippocampal neurons following status epilepticus. Otherwise, downregulation of PGC-1[alpha] by siRNA against pgc-1[alpha] will inhibit VEGF/VEGFR2 (Flk-1) signaling and suppress pro-survival PI3K/AKT and MEK/ERK pathways that are also accompanied by hippocampal CA3 neuronal cell apoptosis. These results may indicate that the PGC-1[alpha] induced VEGF/VEGFR2 pathway may trigger the neuronal survival signaling, and the PI3K/AKT and MEK/ERK signaling pathways. Thus, the axis of PGC-1[alpha]/VEGF/VEGFR2 (Flk-1) and the triggering of downstream PI3K/AKT and MEK/ERK signaling could be considered an endogenous neuroprotective effect against apoptosis in the hippocampus following status epilepticus. Keywords: neuroprotection; PGC-1[alpha]; vascular endothelial growth factor; vascular endothelial growth factor receptor 2; PI3K/AKT; MEK/ERK; status epilepticus; hippocampus
Status epilepticus may cause molecular and cellular events, leading to hippocampal neuronal cell death. Peroxisome proliferator-activated receptor [gamma] coactivator 1-[alpha] (PGC-1[alpha]) is an important regulator of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2), also known as fetal liver kinase receptor 1 (Flk-1). Resveratrol is an activator of PGC-1[alpha]. It has been suggested to provide neuroprotective effects in epilepsy, stroke, and neurodegenerative diseases. In the present study, we used microinjection of kainic acid into the left hippocampal CA3 region in Sprague Dawley rats to induce bilateral prolonged seizure activity. Upregulating the PGC-1[alpha] pathway will increase VEGF/VEGFR2 (Flk-1) signaling and further activate some survival signaling that includes the mitogen activated protein kinase kinase (MEK)/mitogen activated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways and offer neuroprotectionasaconsequence of apoptosis in the hippocampal neurons following status epilepticus. Otherwise, downregulation of PGC-1[alpha] by siRNA against pgc-1[alpha] will inhibit VEGF/VEGFR2 (Flk-1) signaling and suppress pro-survival PI3K/AKT and MEK/ERK pathways that are also accompanied by hippocampal CA3 neuronal cell apoptosis. These results may indicate that the PGC-1[alpha] induced VEGF/VEGFR2 pathway may trigger the neuronal survival signaling, and the PI3K/AKT and MEK/ERK signaling pathways. Thus, the axis of PGC-1[alpha]/VEGF/VEGFR2 (Flk-1) and the triggering of downstream PI3K/AKT and MEK/ERK signaling could be considered an endogenous neuroprotective effect against apoptosis in the hippocampus following status epilepticus. Keywords: neuroprotection; PGC-1[alpha]; vascular endothelial growth factor; vascular endothelial growth factor receptor 2; PI3K/AKT; MEK/ERK; status epilepticus; hippocampus