Novel osmotin attenuates glutamate-induced synaptic dysfunction and neurodegeneration via the JNK/PI3K/Akt pathway in postnatal rat brain.
The glutamate-induced excitotoxicity pathway has been reported in several neurodegenerative diseases. Molecules that inhibit the release of glutamate or cause the overactivation of glutamate receptors can minimize neuronal cell death in these diseases. Osmotin, a homolog of mammalian adiponectin, is a plant protein from Nicotiana tabacum that was examined for the first time in the present study to determine its protective effects against glutamate-induced synaptic dysfunction and neurodegeneration in the rat brain at postnatal day 7. The results indicated that glutamate treatment induced excitotoxicity by overactivating glutamate receptors, causing synaptic dysfunction and neuronal apoptosis after 4 h in the cortex and hippocampus of the postnatal brain. In contrast, post-treatment with osmotin significantly reversed glutamate receptor activation, synaptic deficit and neuronal apoptosis by stimulating the JNK/PI3K/Akt intracellular signaling pathway. Moreover, osmotin treatment abrogated glutamate-induced DNA damage and apoptotic cell death and restored the localization and distribution of p53, p-Akt and caspase-3 in the hippocampus of the postnatal brain. Finally, osmotin inhibited glutamate-induced PI3K-dependent ROS production in vitro and reversed the cell viability decrease, cytotoxicity and caspase-3/7 activation induced by glutamate. Taken together, these results suggest that osmotin might be a novel neuroprotective agent in excitotoxic diseases.
Department of Biology and Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
S A
SA
Shah
Department of Biology and Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
H Y
HY
Lee
Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47907-2010, USA.
R A
RA
Bressan
Department of Biochemistry and Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
D J
DJ
Yun
Department of Biology and Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
M O
MO
Kim
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010940:Plant Proteins / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000502:physiology
D018696:Neuroprotective Agents; D010940:Plant Proteins; C073139:osmotin protein, Nicotiana tabacum; D018698:Glutamic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048670:MAP Kinase Kinase 4