Short-term stimulation of calcium-permeable transient receptor potential canonical 5-containing channels by oxidized phospholipids.
Arterioscler Thromb Vasc Biol
; 30(7): 1453-9, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20378846
ABSTRACT
OBJECTIVE:
To determine whether calcium-permeable channels are targets for the oxidized phospholipids 1-palmitoyl-2-glutaroyl-phosphatidylcholine (PGPC) and 1-palmitoyl-2-oxovaleroyl-phosphatidylcholine (POVPC). METHODS ANDRESULTS:
Oxidized phospholipids are key factors in inflammation and associated diseases, including atherosclerosis; however, the initial reception mechanisms for cellular responses to the factors are poorly understood. Low micromolar concentrations of PGPC and POVPC evoked increases in intracellular calcium in human embryonic kidney 293 cells that overexpressed human transient receptor potential canonical 5 (TRPC5) but not human TRP melastatin (TRPM) 2 or 3. The results of electrophysiological experiments confirmed stimulation of TRPC5. To investigate relevance to endogenous channels, we studied proliferating vascular smooth muscle cells from patients undergoing coronary artery bypass surgery. PGPC and POVPC elicited calcium entry that was inhibited by anti-TRPC5 or anti-TRPC1 antibodies or dominant-negative mutant TRPC5. Calcium release did not occur. The effect was functionally relevant because it enhanced cell migration. The actions of PGPC and POVPC depended on G(i/o) proteins but not on previously identified G protein-coupled receptors for oxidized phospholipids.CONCLUSIONS:
Stimulation of calcium-permeable TRPC5-containing channels may be an early event in cellular responses to oxidized phospholipids that couples to cell migration and requires an unidentified G protein-coupled receptor.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Éteres Fosfolipídicos
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Sinalização do Cálcio
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Miócitos de Músculo Liso
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Canais de Cátion TRPC
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Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article