Lactosylceramide-Induced Phosphorylation Signaling to Group IVA Phospholipase A2 via Reactive Oxygen Species in Tumor Necrosis Factor-α-Treated Cells.
J Cell Biochem
; 118(12): 4370-4382, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28444900
ABSTRACT
The activity of α-type cytosolic phospholipase A2 (cPLA2 α, group IVA PLA2 ), which releases arachidonic acid (AA), is mainly regulated by the Ca2+ -induced intracellular translocation/attachment of the enzyme to substrate membranes and its phosphorylation. We previously reported that tumor necrosis factor-α (TNFα) stimulated the formation of lactosylceramide (LacCer) in L929 fibroblast cells, and this lipid directly bound with and activated cPLA2 α [Nakamura et al. [2013] J. Biol. Chem. 28823264-23272]. We herein investigated the role of phosphorylation signaling in the TNFα/LacCer-induced activation of cPLA2 α in cells. TNFα-treated L929 cells released AA via the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cPLA2 α, while a treatment with LacCer alone released AA in a similar manner. The TNFα-induced responses including release of AA were decreased by the inhibition of LacCer synthesis. The treatment with TNFα and LacCer increased the levels of reactive oxygen species (ROS), and the reduction/scavenging of ROS decreased the phosphorylation cascade and release of AA in TNFα/LacCer-treated L929 cells. In the cell line CHO, the treatment with LacCer stimulated the phosphorylation cascade and release of AA via the formation of ROS. Treatments with the anti-LacCer antibody and 4ß-phorbol 12-myristate 13-acetate stimulated the phosphorylation cascade, but did not release AA by itself. When combined with the Ca2+ ionophore A23187, treatments with the anti-LacCer antibody and 4ß-phorbol 12-myristate 13-acetate released AA. These results, including our previous findings, showed that LacCer alone simultaneously stimulates two processes to activate cPLA2 α a phosphorylation signal and attachment of the enzyme to substrate membranes. J. Cell. Biochem. 118 4370-4382, 2017. © 2017 Wiley Periodicals, Inc.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos CD
/
Fator de Necrose Tumoral alfa
/
Espécies Reativas de Oxigênio
/
Sistema de Sinalização das MAP Quinases
/
Fosfolipases A2 do Grupo IV
/
Fibroblastos
/
Lactosilceramidas
Limite:
Animals
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão