Activation of peroxisome proliferator-activated receptor-δ attenuates glutamate-induced neurotoxicity in HT22 mouse hippocampal cells

• Published in: Journal of neuroscience research Vol. 90; no. 8; pp. 1646 - 1653
• Main Authors: Jin, Hana, Ham, Sun Ah, Kim, Min Young, Woo, Im Sun, Kang, Eun Sil, Hwang, Jung Seok, Lee, Ko-Woon, Kim, Hye Jung, Roh, Gu Seob, Lim, Dae-Seog, Kang, Dawon, Seo, Han Geuk
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2012
• Subjects: Animals; Apoptosis - physiology; Blotting, Western; calcium; Calcium - metabolism; Cell Line; Cell Separation; Excitatory Amino Acids - toxicity; Flow Cytometry; Gene Knockdown Techniques; glutamate; Glutamic Acid - toxicity; Hippocampus - drug effects; Hippocampus - metabolism; HT22 mouse hippocampal cells; Mice; Neurons - metabolism; Oxidative Stress - physiology; peroxisome proliferator-activated receptor-δ; PPAR delta - metabolism; Reactive Oxygen Species - metabolism; RNA, Small Interfering; ROS; Transfection
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.23053

Glutamate‐induced neurotoxicity has been implicated in the pathogenesis of neurodegenerative disorders; however, little is known about the cellular events that underlie neurotoxicity or how to impede these events. This study demonstrates that peroxisome proliferator‐activated receptor (PPAR)‐δ regulates glutamate‐induced neurotoxicity in HT22 mouse hippocampal cells. Activation of PPARδ by GW501516, a specific ligand, significantly inhibited glutamate‐induced cell death and reactive oxygen species (ROS) production in HT22 cells. The siRNA‐mediated knockdown of PPARδ abrogated the effects of GW501516 in neuronal toxicity and ROS production induced by glutamate. In addition, ligand‐activated PPARδ reduced the glutamate‐induced level of intracellular calcium ions (Ca2+) by modulating the influx of Ca2+ from the extracellular space. Similarly, glutamate‐induced cell death and intracellular Ca2+ levels were attenuated in the presence of LY83583, an inhibitor of soluble guanylyl cyclase. Taken together, these results suggest that PPARδ plays an important role in glutamate‐induced neurotoxicity by modulating oxidative stress and Ca2+ influx. © 2012 Wiley Periodicals, Inc.