Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme.

Abstract	Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa-/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa-/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa-/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD.
Authors	Daishi Yui, Yoichiro Nishida, Tomoko Nishina, Kaoru Mogushi, Mio Tajiri, Satoru Ishibashi, Itsuki Ajioka, Kinya Ishikawa, Hidehiro Mizusawa, Shigeo Murayama, Takanori Yokota
Journal	PloS one (PLoS One) Vol. 10 Issue 12 Pg. e0143518 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID	26637123 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins alpha-tocopherol transfer protein Group III Phospholipases A2 PLA2G3 protein, human PLA2G3 protein, mouse Insulysin
Topics	Aging (genetics) Alzheimer Disease (genetics, metabolism) Animals Carrier Proteins (genetics) Cells, Cultured Cerebrum (metabolism) Disease Models, Animal Gene Expression Profiling Gene Knockout Techniques Group III Phospholipases A2 (genetics, metabolism) HEK293 Cells Humans Insulysin (genetics) Mice Oligonucleotide Array Sequence Analysis Organ Specificity Oxidative Stress Up-Regulation

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