Novel lipid networks regulated by the phospholipase A2 family

2014 Fiscal Year Final Research Report

• Project Area: Machineries of bioactive lipids in homeostasis and diseases
• Project/Area Number: 22116005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: MURAKAMI Makoto 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 参事研究員 (60276607)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 酵素 / 脂質 / 生体分子 / 遺伝子 / 細胞・組織 / 遺伝子改変マウス / リピドミクス / 病態

Outline of Final Research Achievements

Phospholipase A2s (PLA2s) are a group of enzymes that hydrolyze the sn-2 position of phospholipids to generate fatty acids and lysophospholipids. Mammalian genomes encode genes for more than 30 PLA2s or related enzymes, which are subdivided into several groups on the basis of their structures and enzymatic properties. In this study, we used transgenic and knockout mice for various PLA2s in combination with lipidomic analyses to decipher their pathophysiological roles and underlying lipid pathways in various pathophysiological events. From this approach, we successfully identified the novel roles of secreted PLA2s in mast cell maturation and allergy (PLA2G3), resolution of contact hypersensitivity (PLA2G2D), metabolic syndrome (PLA2G5 and PLA2G2E), sperm maturation and fertility (PLA2G3 and PLA2G10), and so on. Overall, this study reveal that the sPLA2 family affects various biological events by modulating extracellular phospholipid milieus in response to given microenvironmental cues.

Free Research Field

脂質生物学