title: Plasmalogens rescue neuronal cell death through an activation of AKT and ERK survival signaling.
abstract: Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls), which are glycerophospholipids containing vinyl ether linkage at sn-1 position, can protect the neuronal cell death upon serum deprivation. Interestingly, caspse-9, but not caspase-8 and caspase-12, was cleaved upon the serum starvation in Neuro-2A cells. Pls treatments effectively reduced the activation of caspase-9. Furthermore, cellular signaling experiments showed that Pls enhanced phosphorylation of the phosphoinositide 3-kinase (PI3K)-dependent serine/threonine-specific protein kinase AKT and extracellular-signal-regulated kinases ERK1/2. PI3K/AKT inhibitor LY294002 and MAPK/ERK kinase (MEK) inhibitor U0126 treatments study clearly indicated that Pls-mediated cell survival was dependent on the activation of these kinases. In addition, Pls also inhibited primary mouse hippocampal neuronal cell death induced by nutrient deprivation, which was associated with the inhibition of caspase-9 and caspase-3 cleavages. It was reported that Pls content decreased in the brain of the Alzheimer's patients, which indicated that the reduction of Pls content could endanger neurons. The present findings, taken together, suggest that Pls have an anti-apoptotic action in the brain. Further studies on precise mechanisms of Pls-mediated protection against cell death may lead us to establish a novel therapeutic approach to cure neurodegenerative disorders.
authors.affiliation: Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Md Shamim
authors.initials: MS
authors.lastname: Hossain
authors.affiliation: Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ifuku
authors.affiliation: Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Take
authors.affiliation: Central Research Institute, Marudai Food Co. Ltd., Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kawamura
authors.affiliation: Central Research Institute, Marudai Food Co. Ltd., Osaka, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Miake
authors.affiliation: Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Katafuchi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010955:Plasmalogens / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D010955:Plasmalogens; D014212:Tretinoin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases