Short-term stimulation of calcium-permeable transient receptor potential canonical 5-containing channels by oxidized phospholipids.
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).


RESULTS
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.
Al-Shawaf
Eman
E
Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, England.
Naylor
Jacqueline
J
Taylor
Hilary
H
Riches
Kirsten
K
Milligan
Carol J
CJ
O'Regan
David
D
Porter
Karen E
KE
Li
Jing
J
Beech
David J
DJ
D020013:Calcium Signaling; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010084:Oxidation-Reduction; D010742:Phospholipid Ethers / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; C400185:1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine; D010742:Phospholipid Ethers; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; C475667:TRPM3 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go