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Hydrolysis of Phosphatidylcholine‐Isoprostanes (PtdCho‐IP) by Peripheral Human Group IIA, V and X Secretory Phospholipases A 2 (sPLA 2 )
Author(s) -
Kuksis Arnis,
Pruzanski Waldemar
Publication year - 2017
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-017-4264-z
Subject(s) - phosphatidylcholine , chemistry , incubation , arachidonic acid , hydrolysis , lipid peroxidation , enzyme , biochemistry , medicine , phospholipid , membrane
Biologically active F‐ and E/D‐type‐prostane ring isomers (F 2 ‐IP and E 2 /D 2 ‐IP, respectively) are produced in situ by non‐enzymatic peroxidation of arachidonic acid esterified to GroPCho (PtdCho‐IP) and are universally distributed in tissue lipoproteins and cell membranes. Previous work has shown that platelet‐activating factor acetylhydrolases (PAF‐AH) are the main endogenous PLA 2 involved in degradation of PtdCho‐IP. The present study shows that the PtdCho‐IP are also subject to hydrolysis by group IIA, V and X secretory PLA 2 , which also have a wide peripheral tissue distribution. For this demonstration, we compared the LC/MS profiles of PtdCho‐IP of auto‐oxidized plasma lipoproteins after incubation for 1–4 h (37 °C) in the absence or presence of recombinant human sPLA 2 (1–2.5 µg/ml). In the absence of exogenously added sPLA 2 the total PtdCho‐IP level after 4 h incubation reached 15.9, 21.6 and 8.7 nmol/mg protein of LDL, HDL and HDL 3 , respectively. In the presence of group V or group X sPLA 2 (2.5 µg/ml), the PtdCho‐IP was completely hydrolyzed in 1 h, while in the presence of group IIA sPLA 2 (2.5 µg/ml) the hydrolysis was less than 25% in 4 h, although it was complete after 8–24 h incubation. This report provides the first demonstration that PtdCho‐IP are readily hydrolyzed by group IIA, V and X sPLA 2 . A co‐location of sPLA 2 and the substrates in various tissues has been recorded. Thus, the initiation of interaction and production of isoprostanes in situ are highly probable.