title: Nitric oxide-mediated neuronal apoptosis in rats with recurrent febrile seizures through endoplasmic reticulum stress pathway.
abstract: Nitric oxide (NO), as a neurotransmitter, exerts various physiological and pathological effects on the brain. Excess NO is toxic to neurons and may cause neuronal apoptosis. However, the cascade of NO-mediated apoptosis is not fully understood. We utilized a recurrent febrile seizures (FS) rat model and found that plasma NO was increased, neuronal apoptosis was evident, the expression of glucose-regulated protein78 (GRP78, a well-established marker of ER stress) was elevated, and caspase-12 (an ER stress-specific proapoptosis molecule) was activated in the hippocampus in a time-dependent manner after recurrent FS. Administration of sodium nitroprusside (SNP, an NO donor) enhanced neuronal apoptosis, down-regulated the expression of GRP78, and increased that of caspase-12 in FS+SNP groups compared with FS groups. In contrast, treatment with N(G)-nitrol-l-arginine methyl ester (l-NAME, a competitive NO synthase inhibitor) inhibited neuronal apoptosis, up-regulated the expression of GRP78, and decreased that of caspase-12 in FS+l-NAME groups compared with FS groups. These results suggest that NO mediates neuronal apoptosis caused by recurrent FS, and that the ER stress pathway is involved in NO-mediated neuronal apoptosis.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, People's Republic of China. chenjing5640042@hotmail.com
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jiong
authors.initials: J
authors.lastname: Qin
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Yang
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Chang
authors.forename: Xinna
authors.initials: X
authors.lastname: Ji
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053454:Caspase 12 / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000473:pathology*; D013312:Stress, Physiological; D013997:Time Factors; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053454:Caspase 12; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010751:Phosphopyruvate Hydratase; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP