Global assessment of oxidized free fatty acids in brain reveals an enzymatic predominance to oxidative signaling after trauma

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Article

Anthonymuthu, Tamil S.^1,2,3  Kenny, Elizabeth M.^1,2,3  Amoscato, Andrew A.⁴  Lewis, Jesse^1,2,3  Kochanek, Patrick M.^1,2,5  Kagan, Valerian E.^3,4  Bayir, Hulya^1,2,3,4,5 

[1] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15224 USA

[3] Univ Pittsburgh, Ctr Free Rad & Antioxidant Hlth, Pittsburgh, PA 15219 USA

[4] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Environm & Occupat Hlth, Pittsburgh, PA 15219 USA

[5] Univ Pittsburgh, Childrens Hosp Pittsburgh UPMC, Pittsburgh, PA 15224 USA

关键词: Lipid peroxidation;    Docosanoids;    Eicosanoids;    Octadecanoids;    Cardiolipin;    Pro-resolving mediators;   

DOI  :  10.1016/j.bbadis.2017.03.015

来源: Elsevier

【 摘 要 】

Traumatic brain injury (TBI) is a major health problem associated with significant morbidity and mortality. The pathophysiology of TBI is complex involving signaling through multiple cascades, including lipid peroxidation. Oxidized free fatty acids, a prominent product of lipid peroxidation, are potent cellular mediators involved in induction and resolution of inflammation and modulation of vasomotor tone. While previous studies have assessed lipid peroxidation after TBI, to our knowledge no studies have used a systematic approach to quantify the global oxidative changes in free fatty acids. In this study, we identified and quantified 244 free fatty acid oxidation products using a newly developed global liquid chromatography tandem-mass spectrometry (LC MS/MS) method. This methodology was used to follow the time course of these lipid species in the contusional cortex of our pediatric rat model of TBI. We show that oxidation peaked at 1 h after controlled cortical impact and was progressively attenuated at 4 and 24 h time points. While enzymatic and non-enzymatic pathways were activated at 1 h post-TBI, enzymatic lipid peroxidation was the predominant mechanism with 15-lipoxygenase (LOX) contributing to the majority of total oxidized fatty acid content. Pro-inflammatory lipid mediators were significantly increased at 1 and 4 h after TBI with return to basal levels by 24 h. Anti-inflammatory lipid mediators remained significantly increased across all three time points, indicating an elevated and sustained anti-inflammatory response following TBI.

【 授权许可】

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