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Hydrolysis of Phosphatidylcholine-Isoprostanes (PtdCho-IP) by Peripheral Human Group IIA, V and X Secretory Phospholipases A2 (sPLA2)

  • Original Article
  • Published:
Lipids

Abstract

Biologically active F- and E/D-type-prostane ring isomers (F2-IP and E2/D2-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 PLA2 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 PLA2, 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 sPLA2 (1–2.5 µg/ml). In the absence of exogenously added sPLA2 the total PtdCho-IP level after 4 h incubation reached 15.9, 21.6 and 8.7 nmol/mg protein of LDL, HDL and HDL3, respectively. In the presence of group V or group X sPLA2 (2.5 µg/ml), the PtdCho-IP was completely hydrolyzed in 1 h, while in the presence of group IIA sPLA2 (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 sPLA2. A co-location of sPLA2 and the substrates in various tissues has been recorded. Thus, the initiation of interaction and production of isoprostanes in situ are highly probable.

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Abbreviations

ARA:

Arachidonic acid

CerPCho:

Sphingomyelin

D2/E2-IP:

D2/E2-type prostane ring isomers

F2-IP:

F2-type prostane ring isomers

GroPCho:

Glycerophosphocholine

HDL:

High density lipoprotein

Iso:

Isoprostane

LC/ESI-MS:

Liquid chromatography/electrospray ionization–mass spectrometry

LDL:

Low density lipoprotein

Lp-PLA2 :

Lipoprotein-associated PLA2

LysoPtdCho:

Lysophosphatidylcholine

NP:

Neutral phase

PAF-AH:

Platelet-activating factor acetylhydrolase

PtdCho:

Phosphatidylcholine

PtdEtn:

Phosphatidylethanolamine

PLA2 :

Phospholipase A2

PtdSer:

Phosphatidylserine

PtdCho-IP:

Phosphatidylcholine-isoprostanes

sPLA2 :

Secretory phospholipase A2

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Acknowledgements

This work was supported in whole or in part by Grants from Donnelly Center, University of Toronto (to A.K.) and a Grant from R.E. Court and Co. (to W.P.). The authors wish to thank Drs. Lajos Marai and Amir Ravandi for obtaining the original LC/ESI-MS recordings.

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Authors and Affiliations

  1. Banting and Best Department of Medical Research, Charles H. Best Institute, University of Toronto, 112 College Street, Toronto, ON, M5G 1L6, Canada

    Arnis Kuksis

  2. Department of Medicine, University of Toronto, Toronto, Canada

    Waldemar Pruzanski

  3. Rosedale Medical Centre, 600 Sherbourne St., Suite 602, Toronto, ON, M4X 1W4, Canada

    Waldemar Pruzanski

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  1. Arnis Kuksis
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  2. Waldemar Pruzanski
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Correspondence to Arnis Kuksis.

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Kuksis, A., Pruzanski, W. Hydrolysis of Phosphatidylcholine-Isoprostanes (PtdCho-IP) by Peripheral Human Group IIA, V and X Secretory Phospholipases A2 (sPLA2). Lipids 52, 477–488 (2017). https://doi.org/10.1007/s11745-017-4264-z

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