Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling

International Journal of Molecular Sciences

Tsu-Kung Lin¹  Yao-Chung Chuang¹  Shang-Der Chen¹  Chia-Wei Liou¹  Nai-Ching Chen¹  Shu-Fang Chen¹  Jyun-Bin Huang²  Hsiu-Yung Pan²  Shih-Pin Hsu³  Chung-Yao Hsu⁴  Hung-Yi Chuang⁵  Jie-Hau Li⁶  Xuan-Ping Liu⁶ 

[1] College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;Department of Neurology, E-Da Hospital/School of Medicine, I-Shou University, Kaohsiung 824, Taiwan;Department of Neurology, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital and School of Public Health, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;Institute for Translation Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;

关键词: neuroprotection;    PGC-1α;    vascular endothelial growth factor;    vascular endothelial growth factor receptor 2;    PI3K/AKT;    MEK/ERK;   

DOI  :  10.3390/ijms21197247

来源: DOAJ

【 摘 要 】

Status epilepticus may cause molecular and cellular events, leading to hippocampal neuronal cell death. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) 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-1α. 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-1α 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 neuroprotection as a consequence of apoptosis in the hippocampal neurons following status epilepticus. Otherwise, downregulation of PGC-1α by siRNA against pgc-1α 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-1α induced VEGF/VEGFR2 pathway may trigger the neuronal survival signaling, and the PI3K/AKT and MEK/ERK signaling pathways. Thus, the axis of PGC-1α/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.

【 授权许可】

Unknown