Analyses of phospholipase A_2 enzymes that are involved in signaling and non-signaling events

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More than 20 phospholipase A_2 (PLA_2) enzymes, which hydrolyze the sn-2 position of glycerophospholipids to liberate fatty acids and lysophospholipids, have been identified in mammals. This study aims to clarify the functions of individual PLA_2 enzymes. In this year, we examined the functions of two secretory PLA_2 (sPLA_2) isozymes in vivo using their transgenic (Tg) and knockout (KO) mice.On the basis of our recent finding that group X sPLA_2 (sPLA_2-X) is located in peripheral neuronal fibers, we herein looked for some neuronal phenotypes in sPLA_2-X KO mice. We found that the pain nociception induced by intraperitoneal administration of acetic acid was significantly reduced in sPLA_2-X KO mice as compared with that in replicate wild-type (WT) mice. Conversely, enhanced pain response was observed in sPLA_2-X Tg mice relative to that in WT mice. Immunohistochemistry revealed that the immunoreactive sPLA_2-X staining was found in the sciatic nerve fibers as well as in dorsal root ga … More nglions adjacent to the spinal cord. We therefore speculate that the neuron-associated sPLA_2-X may play a regulatory role in the neuronal transmission through as yet unknown mechanisms.We found that group III sPLA_2 (sPLA_2-III) Tg mice displayed altered plasma lipoprotein composition manifested by decreased HDL and increased modified LDL levels, an event that is generally believed to be linked to atherosclerosis. The view that sPLA_2-III might be involved in the process of atherosclerosis was further supported by immunohistochemical observation that sPLA_2-III immunoreactivity was found in the atherosclerotic lesions in humans as well as those in apoE-deficicent mice. Moreover, sPLA_2-III Tg mice fed with high-fat diet exhibited obesity relative to replicate WT mice. In addition to these metabolic syndrome-like phenotypes, passive cutaneous anaphylactic reaction was elevated in sPLA_2-III Tg mice relative to replicate WT mice, and splenomegaly and dermatitis occurred spontaneously and progressively in aged sPLA_2-III Tg mice, suggesting unexplored actions of sPLA_2-III on the immune system. Finally, we have succeeded in generating sPLA_2-III-deficient mice, which will unveil the physiological relevance of the aforementioned pathogenic aspects observed in sPLA_2-III Tg mice. Less