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Sphingomyelin Regulates the Activity of Secretory Phospholipase A 2 in the Plasma Membrane
Author(s) -
Nakamura Hiroyuki,
Wakita Shigeo,
Yasufuku Kana,
Makiyama Tomohiko,
Waraya Misa,
Hashimoto Naohiro,
Murayama Toshihiko
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25145
Subject(s) - sphingomyelin , sphingolipid , chinese hamster ovary cell , endosome , npc1 , biology , sphingomyelin phosphodiesterase , arachidonic acid , acid sphingomyelinase , ceramide , cell culture , in vitro , biochemistry , microbiology and biotechnology , cell , cholesterol , enzyme , apoptosis , genetics
We examined the effect of the cellular sphingolipid level on the release of arachidonic acid (AA) and the activity of secretory phospholipase A 2 (sPLA 2 ) using two Chinese hamster ovary (CHO)‐K1 cell mutants, LY‐B and LY‐A cells, deficient in sphingolipid synthesis. In LY‐B cells, deficiency of sphingolipids enhanced the release of AA induced by bee venom sPLA 2 ‐III or human sPLA 2 ‐V. These alterations were reversed by replenishment of exogenous sphingomyelin (SM). In LY‐A cells, deficiency of SM increased the release of AA induced by sPLA 2 . In CHO‐K1 cells, decrease and increase of SM level in the plasma membrane by pharmacological methods increased and inhibited the release of AA, respectively. SM inhibited the activity of sPLA 2 in vitro. Niemann‐Pick disease type C (NPC) is a lysosomal storage disorder caused by mutation of either the NPC1 or NPC2 gene, and is characterized by accumulation of cholesterol and sphingolipids including SM in late endosomes/lysosomes. Increased levels of AA and sPLA 2 activity are involved in various neurodegenerative diseases. In CHO cells lacking NPC1 (A101 cells), SM level was lower in the plasma membrane, while it was higher in late endosomes/lysosomes. The release of AA induced by sPLA 2 was increased in A101 cells than that in parental cells (JP17 cells), which was attenuated by adding exogenous SM. In addition, sPLA 2 ‐III‐induced cytotoxicity in A101 cells was much higher than that in JP17 cells. These results suggest that SM in the plasma membrane plays important roles in regulating sPLA 2 activity and the enzyme‐induced cytotoxicity in A101 cells. J. Cell. Biochem. 116: 1898–1907, 2015. © 2015 Wiley Periodicals, Inc.