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Activation of peroxisome proliferator‐activated receptor‐δ attenuates glutamate‐induced neurotoxicity in HT22 mouse hippocampal cells
Author(s) -
Jin Hana,
Ham Sun Ah,
Kim Min Young,
Woo Im Sun,
Kang Eun Sil,
Hwang Jung Seok,
Lee KoWoon,
Kim Hye Jung,
Roh Gu Seob,
Lim DaeSeog,
Kang Dawon,
Seo Han Geuk
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23053
Subject(s) - neurotoxicity , glutamate receptor , microbiology and biotechnology , chemistry , peroxisome proliferator activated receptor , intracellular , receptor , calcium in biology , extracellular , oxidative stress , reactive oxygen species , pharmacology , biochemistry , biology , toxicity , organic chemistry
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. © 2012 Wiley Periodicals, Inc.