Abstract
345 - Catecholamine Metabolism via Monoamine Oxidase Disrupts Oxidative Phosphorylation Efficiency in Glutathione Peroxidase-4 Deficient Mouse and Human Myocardium
Free radical biology & medicine, Vol.100, pp.S147-S147
11/2016
DOI: 10.1016/j.freeradbiomed.2016.10.386
Abstract
Glutathione peroxidase-4 (GPx4) is a selenoenzyme expressed in mitochondria and nuclear compartments which exclusively neutralizes lipid peroxides. Monoamine oxidase (MAO), an outer mitochondrial membrane-bound enzyme responsible for catecholamine metabolism, produces a reactive catechol-aldehyde and H2O2 upon substrate deamination. Current findings in human myocardial samples from our lab show that obese/diabetic patients exhibit greater maximal MAO activity and content, but lower GPx4 compared with nondiabetic patients, suggesting that both increased MAO and decreased GPx4 act to compound levels of reactive aldehyde species in diabetic myocardium. Our preliminary experiments using nitro blue tetrazolium staining have revealed protein modification by catechol-aldehydes derived from norepinephrine (NE) and dopamine (DA) in whole heart lysate and isolated cardiac mitochondria from mice and humans, an effect mitigated by MAO inhibitors. We further examined the effects of catecholamine metabolism via MAO on ATP production and O2 consumption (OxPhos) in isolated cardiac mitochondria prepared from WT and GPx4-deficient (GPx4+/-) mice, and in permeabilized myofibers prepared from human atrial myocardium. Both DA and NE significantly decreased ATP production and O2 consumption in GPx4+/- mice, but not WT, by 15% and 13%, respectively (p<0.05). Furthermore, the ATP/O ratio, an indicator of OxPhos efficiency, was also reduced in the GPx4+/- mice. In human atrial myocardium (n=11), NE significantly decreased ATP/O by ~35% (p<0.05), which was attenuated by MAO inhibitors. This translational study provides evidence that 1) catechol-aldehydes are a unique form of oxidative post-translational modification in the heart, and 2) hearts with diminished lipid peroxide-scavenging capacity (e.g., obese/diabetic patients) are more susceptible to catecholamine-induced disruption of mitochondrial OxPhos via MAO.
Details
- Title: Subtitle
- 345 - Catecholamine Metabolism via Monoamine Oxidase Disrupts Oxidative Phosphorylation Efficiency in Glutathione Peroxidase-4 Deficient Mouse and Human Myocardium
- Creators
- Margaret Nelson - East Carolina UniversityEthan J Anderson - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Free radical biology & medicine, Vol.100, pp.S147-S147
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.freeradbiomed.2016.10.386
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Language
- English
- Date published
- 11/2016
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984366303102771
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