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Modulation of the activity of cytosolic phospholipase A2alpha (cPLA2alpha) by cellular sphingolipids and inhibition of cPLA2alpha by sphingomyelin.
J Lipid Res 2010; 51(4):720-8JL

Abstract

We examined the effect of the cellular sphingolipid level on the release of arachidonic acid (AA) and activity of cytosolic phospholipase A2alpha (cPLA2alpha) using two Chinese hamster ovary (CHO)-K1-derived mutants deficient in sphingolipid synthesis: LY-B cells defective in the LCB1 subunit of serine palmitoyltransferase for de novo synthesis of sphingolipid species, and LY-A cells defective in the ceramide transfer protein CERT for SM synthesis. When LY-B and LY-A cells were cultured in Nutridoma medium and the sphingolipid level was reduced, the release of AA stimulated by the Ca(2+) ionophore A23187 increased 2-fold and 1.7-fold, respectively, compared with that from control cells. The enhancement in LY-B cells was decreased by adding sphingosine and treatment with the cPLA2alpha inhibitor. When CHO cells were treated with an acid sphingomyelinase inhibitor to increase the cellular SM level, the release of AA induced by A23187 or PAF was decreased. In vitro studies were then conducted to test whether SM interacts directly with cPLA2alpha. Phosphatidylcholine vesicles containing SM reduced cPLA2alpha activity. Furthermore, SM disturbed the binding of cPLA2alpha to glycerophospholipids. These results suggest that SM at the biomembrane plays important roles in regulating the cPLA2alpha-dependent release of AA by inhibiting the binding of cPLA2alpha to glycerophospholipids.

Authors+Show Affiliations

Laboratory of Chemical Pharmacology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan. ropi@p.chiba-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19965591

Citation

Nakamura, Hiroyuki, et al. "Modulation of the Activity of Cytosolic Phospholipase A2alpha (cPLA2alpha) By Cellular Sphingolipids and Inhibition of cPLA2alpha By Sphingomyelin." Journal of Lipid Research, vol. 51, no. 4, 2010, pp. 720-8.
Nakamura H, Wakita S, Suganami A, et al. Modulation of the activity of cytosolic phospholipase A2alpha (cPLA2alpha) by cellular sphingolipids and inhibition of cPLA2alpha by sphingomyelin. J Lipid Res. 2010;51(4):720-8.
Nakamura, H., Wakita, S., Suganami, A., Tamura, Y., Hanada, K., & Murayama, T. (2010). Modulation of the activity of cytosolic phospholipase A2alpha (cPLA2alpha) by cellular sphingolipids and inhibition of cPLA2alpha by sphingomyelin. Journal of Lipid Research, 51(4), pp. 720-8. doi:10.1194/jlr.M002428.
Nakamura H, et al. Modulation of the Activity of Cytosolic Phospholipase A2alpha (cPLA2alpha) By Cellular Sphingolipids and Inhibition of cPLA2alpha By Sphingomyelin. J Lipid Res. 2010;51(4):720-8. PubMed PMID: 19965591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of the activity of cytosolic phospholipase A2alpha (cPLA2alpha) by cellular sphingolipids and inhibition of cPLA2alpha by sphingomyelin. AU - Nakamura,Hiroyuki, AU - Wakita,Shigeo, AU - Suganami,Akiko, AU - Tamura,Yutaka, AU - Hanada,Kentaro, AU - Murayama,Toshihiko, Y1 - 2009/10/16/ PY - 2009/12/8/entrez PY - 2009/12/8/pubmed PY - 2010/10/13/medline SP - 720 EP - 8 JF - Journal of lipid research JO - J. Lipid Res. VL - 51 IS - 4 N2 - We examined the effect of the cellular sphingolipid level on the release of arachidonic acid (AA) and activity of cytosolic phospholipase A2alpha (cPLA2alpha) using two Chinese hamster ovary (CHO)-K1-derived mutants deficient in sphingolipid synthesis: LY-B cells defective in the LCB1 subunit of serine palmitoyltransferase for de novo synthesis of sphingolipid species, and LY-A cells defective in the ceramide transfer protein CERT for SM synthesis. When LY-B and LY-A cells were cultured in Nutridoma medium and the sphingolipid level was reduced, the release of AA stimulated by the Ca(2+) ionophore A23187 increased 2-fold and 1.7-fold, respectively, compared with that from control cells. The enhancement in LY-B cells was decreased by adding sphingosine and treatment with the cPLA2alpha inhibitor. When CHO cells were treated with an acid sphingomyelinase inhibitor to increase the cellular SM level, the release of AA induced by A23187 or PAF was decreased. In vitro studies were then conducted to test whether SM interacts directly with cPLA2alpha. Phosphatidylcholine vesicles containing SM reduced cPLA2alpha activity. Furthermore, SM disturbed the binding of cPLA2alpha to glycerophospholipids. These results suggest that SM at the biomembrane plays important roles in regulating the cPLA2alpha-dependent release of AA by inhibiting the binding of cPLA2alpha to glycerophospholipids. SN - 1539-7262 UR - https://www.unboundmedicine.com/medline/citation/19965591/Modulation_of_the_activity_of_cytosolic_phospholipase_A2alpha__cPLA2alpha__by_cellular_sphingolipids_and_inhibition_of_cPLA2alpha_by_sphingomyelin_ L2 - http://www.jlr.org/cgi/pmidlookup?view=long&pmid=19965591 DB - PRIME DP - Unbound Medicine ER -