Activation of CTP:phosphocholine cytidylyltransferase by hypochlorite-oxidized phosphatidylcholines

CTP:Phosphocholine Cytidylyltransferase Activation by Oxidized Phosphatidylcholines Correlates with a Decrease in Lipid Order: A 2H NMR Analysis

“…Oxidation of PL 3 PC activated CT 1.6-fold; oxidation of PAPC activated CT 2.1-fold, which is the same degree of activation obtained with egg PC/oleic acid (1/1) sonicated vesicles, i.e., maximal activity (15,17). These results are consistent with our earlier observations using hypochloriteoxidized phospholipids (12). Since oxidized PAPC had the greatest effect on CT activity, PAPC was used in the remainder of this study.…”

“…The activation of CT by oxidized PC is not due to an interaction of an oxidized PC molecule with a specific binding pocket within CT. CT can be activated by dihy-droxyPAPC as shown in the present study, and by hypochlorous acid-oxidized PAPC (12), which generates predominantly hypochlorite adducts at double bond positions. Thus, the nature of the polar adduct on the acyl chain is not critical for the activation of CT.…”

“…Miscellaneous Assays. CT actiVity assay was carried out as described previously (12). The concentration of MLVs in the assay was 1 mM.…”

“…Recently, we showed that hypochlorite-oxidized PCs activate CTP:phosphocholine cytidylyltransferase (CT), a key regulatory enzyme in PC synthesis (12). CT activation by 1 Abbreviations: PC, phosphatidylcholine; CT, CTP:phosphocholine cytidylyltransferase; SUVs, small unilamellar vesicles; MLVs, multilamellar vesicles; PAPC, 1-palmitoyl-2-arachidonoylphosphatidylcholine; PL3PC, 1-palmitoyl-2-linolenoylphosphatidylcholine; PL2PC, 1-palmitoyl-2-linoleoylphosphatidylcholine; POPC, 1-palmitoyl-2-oleoylphosphatidylcholine; DL2PC, dilinoleoylphosphatidylcholine; 31d-PAPC, PAPC perdeuterated on the palmitoyl chain; SM, egg sphingomyelin; PC/O (1:1), egg PC/oleic acid (1:1); LOX-PAPC, lipoxidaseoxidized PAPC; dihydroxyPAPC, oxidized membrane PCs may contribute, in addition to PLA 2 (9), to the repair of ROS-damaged membranes.…”

The anti-tumor drug 2-hydroxyoleic acid (Minerval) stimulates signaling and retrograde transport

“…Such factors would weaken the lipid-lipid interactions, and thus promote intercalation of amphipathic helices of peripheral membrane proteins into the bilayer. As an example, membrane binding of the amphitropic protein CTP:phosphocholine cytidylyltransferase is promoted by factors that increase the phospholipid head group spacing, such as high curvature, the presence of fatty acids or DAG, which both have small “head groups”, and the presence of phospholipids with oxidized acyl chains [45]. As our lipidomics-data revealed that OA was incorporated into complex lipids to a much higher extent than OHOA, it seems unlikely that the cis -unsaturated fatty acid tail of OHOA is solely responsible for our observed phenotypes.…”