Fatty acid nitroalkenes induce resistance to ischemic cardiac injury by modulating mitochondrial respiration at complex II

Jeffrey R. Koenitzer; Gustavo Bonacci; Steven R. Woodcock; Chen Shan Chen; Nadiezhda Cantu-Medellin; Eric E. Kelley; Francisco J. Schopfer

doi:10.1016/j.redox.2015.11.002

Fatty acid nitroalkenes induce resistance to ischemic cardiac injury by modulating mitochondrial respiration at complex II

Jeffrey R. Koenitzer, Gustavo Bonacci, Steven R. Woodcock, Chen Shan Chen, Nadiezhda Cantu-Medellin, Eric E. Kelley, Francisco J. Schopfer

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Nitro-fatty acids (NO₂-FA) are metabolic and inflammatory-derived electrophiles that mediate pleiotropic signaling actions. It was hypothesized that NO₂-FA would impact mitochondrial redox reactions to induce tissue-protective metabolic shifts in cells. Nitro-oleic acid (OA-NO₂) reversibly inhibited complex II-linked respiration in isolated rat heart mitochondria in a pH-dependent manner and suppressed superoxide formation. Nitroalkylation of Fp subunit was determined by BME capture and the site of modification by OA-NO₂ defined by mass spectrometric analysis. These effects translated into reduced basal and maximal respiration and favored glycolytic metabolism in H9C2 cardiomyoblasts as assessed by extracellular H⁺ and O₂ flux analysis. The perfusion of NO₂-FA induced acute cardioprotection in an isolated perfused heart ischemia/reperfusion (IR) model as evidenced by significantly higher rate-pressure products. Together these findings indicate that NO₂-FA can promote cardioprotection by inducing a shift from respiration to glycolysis and suppressing reactive species formation in the post-ischemic interval.

Original language	English
Pages (from-to)	1-10
Number of pages	10
Journal	Redox Biology
Volume	8
DOIs	https://doi.org/10.1016/j.redox.2015.11.002
State	Published - Aug 1 2016

Keywords

Electrophile
Inflammation
Mitochondria
Nitro-fatty acid
Nitroalkene

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10.1016/j.redox.2015.11.002

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title = "Fatty acid nitroalkenes induce resistance to ischemic cardiac injury by modulating mitochondrial respiration at complex II",

abstract = "Nitro-fatty acids (NO2-FA) are metabolic and inflammatory-derived electrophiles that mediate pleiotropic signaling actions. It was hypothesized that NO2-FA would impact mitochondrial redox reactions to induce tissue-protective metabolic shifts in cells. Nitro-oleic acid (OA-NO2) reversibly inhibited complex II-linked respiration in isolated rat heart mitochondria in a pH-dependent manner and suppressed superoxide formation. Nitroalkylation of Fp subunit was determined by BME capture and the site of modification by OA-NO2 defined by mass spectrometric analysis. These effects translated into reduced basal and maximal respiration and favored glycolytic metabolism in H9C2 cardiomyoblasts as assessed by extracellular H+ and O2 flux analysis. The perfusion of NO2-FA induced acute cardioprotection in an isolated perfused heart ischemia/reperfusion (IR) model as evidenced by significantly higher rate-pressure products. Together these findings indicate that NO2-FA can promote cardioprotection by inducing a shift from respiration to glycolysis and suppressing reactive species formation in the post-ischemic interval.",

keywords = "Electrophile, Inflammation, Mitochondria, Nitro-fatty acid, Nitroalkene",

author = "Koenitzer, {Jeffrey R.} and Gustavo Bonacci and Woodcock, {Steven R.} and Chen, {Chen Shan} and Nadiezhda Cantu-Medellin and Kelley, {Eric E.} and Schopfer, {Francisco J.}",

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year = "2016",

month = aug,

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doi = "10.1016/j.redox.2015.11.002",

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AU - Koenitzer, Jeffrey R.

AU - Bonacci, Gustavo

AU - Woodcock, Steven R.

AU - Chen, Chen Shan

AU - Cantu-Medellin, Nadiezhda

AU - Kelley, Eric E.

AU - Schopfer, Francisco J.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Nitro-fatty acids (NO2-FA) are metabolic and inflammatory-derived electrophiles that mediate pleiotropic signaling actions. It was hypothesized that NO2-FA would impact mitochondrial redox reactions to induce tissue-protective metabolic shifts in cells. Nitro-oleic acid (OA-NO2) reversibly inhibited complex II-linked respiration in isolated rat heart mitochondria in a pH-dependent manner and suppressed superoxide formation. Nitroalkylation of Fp subunit was determined by BME capture and the site of modification by OA-NO2 defined by mass spectrometric analysis. These effects translated into reduced basal and maximal respiration and favored glycolytic metabolism in H9C2 cardiomyoblasts as assessed by extracellular H+ and O2 flux analysis. The perfusion of NO2-FA induced acute cardioprotection in an isolated perfused heart ischemia/reperfusion (IR) model as evidenced by significantly higher rate-pressure products. Together these findings indicate that NO2-FA can promote cardioprotection by inducing a shift from respiration to glycolysis and suppressing reactive species formation in the post-ischemic interval.

AB - Nitro-fatty acids (NO2-FA) are metabolic and inflammatory-derived electrophiles that mediate pleiotropic signaling actions. It was hypothesized that NO2-FA would impact mitochondrial redox reactions to induce tissue-protective metabolic shifts in cells. Nitro-oleic acid (OA-NO2) reversibly inhibited complex II-linked respiration in isolated rat heart mitochondria in a pH-dependent manner and suppressed superoxide formation. Nitroalkylation of Fp subunit was determined by BME capture and the site of modification by OA-NO2 defined by mass spectrometric analysis. These effects translated into reduced basal and maximal respiration and favored glycolytic metabolism in H9C2 cardiomyoblasts as assessed by extracellular H+ and O2 flux analysis. The perfusion of NO2-FA induced acute cardioprotection in an isolated perfused heart ischemia/reperfusion (IR) model as evidenced by significantly higher rate-pressure products. Together these findings indicate that NO2-FA can promote cardioprotection by inducing a shift from respiration to glycolysis and suppressing reactive species formation in the post-ischemic interval.

KW - Electrophile

KW - Inflammation

KW - Mitochondria

KW - Nitro-fatty acid

KW - Nitroalkene

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DO - 10.1016/j.redox.2015.11.002

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AN - SCOPUS:84951147710

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VL - 8

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JO - Redox Biology

JF - Redox Biology

ER -

Fatty acid nitroalkenes induce resistance to ischemic cardiac injury by modulating mitochondrial respiration at complex II

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Keywords

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