Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Oxidative lipidomics of hyperoxic acute lung injury: Mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation

Tyurina, YY and Tyurin, VA and Kaynar, M and Kapralova, VI and Wasserloos, K and Li, J and Mosher, M and Wright, L and Wipf, P and Watkins, S and Pitt, BR and Kagan, VE (2010) Oxidative lipidomics of hyperoxic acute lung injury: Mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation. American Journal of Physiology - Lung Cellular and Molecular Physiology, 299 (1). ISSN 1040-0605

[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

Reactive oxygen species have been shown to play a significant role in hyperoxia-induced acute lung injury, in part, by inducing apoptosis of pulmonary endothelium. However, the signaling roles of phospholipid oxidation products in pulmonary endothelial apoptosis have not been studied. Using an oxidative lipidomics approach, we identified individual molecular species of phospholipids involved in the apoptosis-associated peroxidation process in a hyperoxic lung. C57BL/6 mice were killed 72 h after exposure to hyperoxia (100% oxygen). We found that hyperoxia-induced apoptosis (documented by activation of caspase-3 and -7 and histochemical terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining of pulmonary endothelium) was accompanied by nonrandom oxidation of pulmonary lipids. Two anionic phospholipids, mitochondria-specific cardiolipin (CL) and extramitochondrial phosphatidylserine (PS), were the two major oxidized phospholipids in hyperoxic lung. Using electrospray ionization mass spectrometry, we identified several oxygenation products in CL and PS. Quantitative assessments revealed a significant decrease of CL and PS molecular species containing C18:2, C20:4, C22:5, and C22:6 fatty acids. Similarly, exposure of mouse pulmonary endothelial cells (MLEC) to hyperoxia (95% oxygen; 72 h) resulted in activation of caspase-3 and -7 and significantly decreased the content of CL molecular species containing C18:2 and C20:4 as well as PS molecular species containing C22:5 and C22:6. Oxygenated molecular species were found in the same two anionic phospholipids, CL and PS, in MLEC exposed to hyperoxia. Treatment of MLEC with a mitochondria-targeted radical scavenger, a conjugate of hemi-gramicidin S with nitroxide, XJB-5-131, resulted in significantly lower oxidation of both CL and PS and a decrease in hyperoxia-induced changes in caspase-3 and -7 activation. We speculate that cytochrome c driven oxidation of CL and PS is associated with the signaling role of these oxygenated species participating in the execution of apoptosis and clearance of pulmonary endothelial cells, thus contributing to hyperoxic lung injury. Copyright © 2010 the American Physiological Society.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tyurina, YYyyt1@pitt.eduYYT1
Tyurin, VAvtyurin@pitt.eduVTYURIN
Kaynar, M
Kapralova, VI
Wasserloos, K
Li, J
Mosher, M
Wright, L
Wipf, Ppwipf@pitt.eduPWIPF
Watkins, S
Pitt, BRbrucep@pitt.eduBRUCEP
Kagan, VEkagan@pitt.eduKAGAN
Date: 1 July 2010
Date Type: Publication
Journal or Publication Title: American Journal of Physiology - Lung Cellular and Molecular Physiology
Volume: 299
Number: 1
DOI or Unique Handle: 10.1152/ajplung.00035.2010
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 1040-0605
MeSH Headings: Acute Lung Injury--metabolism; Animals; Cardiolipins--chemistry; Cardiolipins--metabolism; Caspases--metabolism; Hyperoxia--metabolism; Hyperoxia--pathology; Lipid Metabolism; Lipid Peroxidation; Lipids--chemistry; Lung--chemistry; Lung--metabolism; Male; Mice; Mice, Inbred C57BL; Oxidation-Reduction; Phosphatidylserines--chemistry; Phosphatidylserines--metabolism; Spectrometry, Mass, Electrospray Ionization
Other ID: NLM PMC2904094
PubMed Central ID: PMC2904094
PubMed ID: 20418384
Date Deposited: 28 May 2013 15:29
Last Modified: 16 Sep 2020 13:55
URI: http://d-scholarship.pitt.edu/id/eprint/18778

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item