title: Activation of peroxisome proliferator-activated receptor-δ attenuates glutamate-induced neurotoxicity in HT22 mouse hippocampal cells.
abstract: 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 (Ca(2+)) by modulating the influx of Ca(2+) from the extracellular space. Similarly, glutamate-induced cell death and intracellular Ca(2+) 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 Ca(2+) influx.
authors.affiliation: Department of Pharmacology, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Jin
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Ham
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Im Sun
authors.initials: IS
authors.lastname: Woo
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kang
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Hwang
authors.forename: Ko-Woon
authors.initials: KW
authors.lastname: Lee
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.forename: Dae-Seog
authors.initials: DS
authors.lastname: Lim
authors.forename: Dawon
authors.initials: D
authors.lastname: Kang
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002469:Cell Separation; D018846:Excitatory Amino Acids / Q000633:toxicity*; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D047494:PPAR delta / Q000378:metabolism*; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
chemical_list: D018846:Excitatory Amino Acids; D047494:PPAR delta; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D002118:Calcium