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Article

Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster

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Departments of Nutrition Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Department of Kinesiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Department of Physical Therapy, Mercer University, Atlanta, GA 30341, USA
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Department of Pathology, University of Washington, Seattle, WA 98195, USA
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Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
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Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA
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Department of Pharmaceutical, Social and Administrative Sciences, Samford University, Birmingham, AL 35229, USA
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Pharmaceutical Sciences Research Institute, Samford University, Birmingham, AL 35229, USA
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Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35233, USA
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Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine, Baltimore, MD 21234, USA
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Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, WA 98195, USA
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Department of Biology, University of Washington, Seattle, WA 98195, USA
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3351; https://doi.org/10.3390/ijms19113351
Received: 6 October 2018 / Revised: 18 October 2018 / Accepted: 24 October 2018 / Published: 26 October 2018
(This article belongs to the Section Biochemistry)
The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug’s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism. View Full-Text
Keywords: aging; angiotensin-converting enzyme inhibitors; nutrient metabolism; genetic background; nutritional stress aging; angiotensin-converting enzyme inhibitors; nutrient metabolism; genetic background; nutritional stress
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MDPI and ACS Style

Ederer, K.A.; Jin, K.; Bouslog, S.; Wang, L.; Gorman, G.S.; Rowe, G.C.; Abadir, P.; Raftery, D.; Moellering, D.; Promislow, D.; Jumbo-Lucioni, P.; De Luca, M. Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster. Int. J. Mol. Sci. 2018, 19, 3351. https://doi.org/10.3390/ijms19113351

AMA Style

Ederer KA, Jin K, Bouslog S, Wang L, Gorman GS, Rowe GC, Abadir P, Raftery D, Moellering D, Promislow D, Jumbo-Lucioni P, De Luca M. Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster. International Journal of Molecular Sciences. 2018; 19(11):3351. https://doi.org/10.3390/ijms19113351

Chicago/Turabian Style

Ederer, Karis A., Kelly Jin, Sarah Bouslog, Lu Wang, Gregory S. Gorman, Glenn C. Rowe, Peter Abadir, Daniel Raftery, Douglas Moellering, Daniel Promislow, Patricia Jumbo-Lucioni, and Maria De Luca. 2018. "Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster" International Journal of Molecular Sciences 19, no. 11: 3351. https://doi.org/10.3390/ijms19113351

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