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Protective effects of placental growth factor on retinal neuronal cell damage
Author(s) -
Inoue Yuki,
Shimazawa Masamitsu,
Nakamura Shinsuke,
Imamura Tomoyo,
Sugitani Sou,
Tsuruma Kazuhiro,
Hara Hideaki
Publication year - 2014
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.23316
Subject(s) - placental growth factor , programmed cell death , ly294002 , apoptosis , neuroprotection , microbiology and biotechnology , pi3k/akt/mtor pathway , vascular endothelial growth factor , biology , cancer research , pharmacology , biochemistry , vegf receptors
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family. Although it has been reported that PlGF protects against neuronal damage in the brain, little is known about the effects of PlGF in the retina. Therefore, we investigated the effects of PlGF on retinal neuronal cells. To evaluate the effects of PlGF against L‐buthionine‐(S,R)‐sulfoximine (BSO)/glutamate cell death, oxygen–glucose deprivation (OGD)‐induced cell death, and light‐induced cell death, RGC‐5 and 661W cells were used. We evaluated the mechanism responsible for the protective effects of PlGF against retinal neuronal cell death by performing the examinations with U1026, which is a mitogen‐activated protein kinase (MEK) inhibitor, and LY294002, which is a phosphoinositide 3‐kinase (PI3K) inhibitor. In addition, we measured caspase‐3/7 activity in RGC‐5 cells and 661W cells. PlGF protected against RGC‐5 cell death induced by BSO/glutamate and OGD and against 661W cell death induced by light irradiation. Moreover, an anti‐PlGF antibody negated these protective effects. The protective effects of PlGF against OGD‐induced RGC‐5 cell death and light‐induced 661W cell death were suppressed by using an anti‐PlGF antibody, U1026, and LY294002. Treatment with PlGF suppressed caspase‐3/7 activity in both cell lines. We demonstrated for the first time that PlGF exerts a protective effect by inhibiting the activation of caspase‐3/7 through the MEK and PI3K pathway in retinal neuronal cells. These data suggest that PlGF may be an important protective factor in the retina. © 2013 Wiley Periodicals, Inc.