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Neuroreport
2022 Oct 12;3315:635-640. doi: 10.1097/WNR.0000000000001828.
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Enhancing oxidative phosphorylation over glycolysis for energy production in cultured mesenchymal stem cells.
Monsour M
,
Gorsky A
,
Nguyen H
,
Castelli V
,
Lee JY
,
Borlongan CV
.
Abstract
OBJECTIVE: Strokes represent as one of the leading causes of death and disability in the USA, however, there is no optimal treatment to reduce the occurrence or improve prognosis. Preconditioning of tissues triggers ischemic tolerance, a physiological state that may involve a metabolic switch (i.e. from glycolysis to oxidative phosphorylation or OxPhos) to preserve tissue viability under an ischemic insult. Here, we hypothesized that metabolic switching of energy source from glucose to galactose in cultured mesenchymal stem cells (MSCs) stands as an effective OxPhos-enhancing strategy.
METHODS: MSCs were grown under ambient condition (normal MSCs) or metabolic switching paradigm (switched MSCs) and then assayed for oxygen consumption rates (OCR) and extracellular acidification rate (ECAR) using the Seahorse technology to assess mitochondrial respiration.
RESULTS: Normal MSCs showed a lower OCR/ECAR ratio than switched MSCs at baseline (P < 0.0001), signifying that there were greater levels of OxPhos compared to glycolysis in switched MSCs. By modulating the mitochondrial metabolism with oligomycin (time points 4-6), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (7-9), and rotenone and antimycin (time points 10-12), switched MSCs greater reliance on OxPhos was further elucidated (time points 5-12; P < 0.0001; time point 4; P < 0.001).
CONCLUSION: The metabolic switch from glycolytic to oxidative metabolism amplifies the OxPhos potential of MSCs, which may allow these cells to afford more robust therapeutic effects against neurological disorders that benefit from ischemic tolerance.
Anthony,
Neuroinflammation, Stem Cells, and Stroke.
2022, Pubmed
Anthony,
Neuroinflammation, Stem Cells, and Stroke.
2022,
Pubmed
Conte,
Galactose in human metabolism, glycosylation and congenital metabolic diseases: Time for a closer look.
2021,
Pubmed
Cumbler,
In-Hospital Ischemic Stroke.
2015,
Pubmed
Dar,
Bioenergetic Adaptations in Chemoresistant Ovarian Cancer Cells.
2017,
Pubmed
Divakaruni,
Analysis and interpretation of microplate-based oxygen consumption and pH data.
2014,
Pubmed
Fiorenza,
High-intensity exercise training enhances mitochondrial oxidative phosphorylation efficiency in a temperature-dependent manner in human skeletal muscle: implications for exercise performance.
2019,
Pubmed
Francis,
Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning.
2010,
Pubmed
Hacke,
Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.
2008,
Pubmed
Hayakawa,
Transfer of mitochondria from astrocytes to neurons after stroke.
2016,
Pubmed
Kase,
Remodeling of oxidative energy metabolism by galactose improves glucose handling and metabolic switching in human skeletal muscle cells.
2013,
Pubmed
Koton,
Stroke incidence and mortality trends in US communities, 1987 to 2011.
2014,
Pubmed
Murry,
Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode.
1990,
Pubmed
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group,
Tissue plasminogen activator for acute ischemic stroke.
1995,
Pubmed
Nguyen,
Eye Opener in Stroke.
2019,
Pubmed
Ovbiagele,
Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association.
2013,
Pubmed
Qu,
The ketogenic diet as a therapeutic intervention strategy in mitochondrial disease.
2021,
Pubmed
Redman,
Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes.
2011,
Pubmed
Rose,
Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort.
2014,
Pubmed
Srivastava,
The Mitochondrial Basis of Aging and Age-Related Disorders.
2017,
Pubmed
Sun,
The Mitochondrial Basis of Aging.
2016,
Pubmed
Vidali,
Mitochondria: The ketogenic diet--A metabolism-based therapy.
2015,
Pubmed
Wang,
The role of mitochondria in apoptosis*.
2009,
Pubmed
Yetkin-Arik,
The role of glycolysis and mitochondrial respiration in the formation and functioning of endothelial tip cells during angiogenesis.
2019,
Pubmed
Zhang,
Measuring energy metabolism in cultured cells, including human pluripotent stem cells and differentiated cells.
2012,
Pubmed
Zuurveld,
Oxidative metabolism of cultured human skeletal muscle cells in comparison with biopsy material.
1985,
Pubmed
