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bioRxiv · 10.1101/2024.06.03.597148

GCN5L1 regulates glucose and ketone body metabolism during cardiac ischemia-reperfusion injury

Bugga, P.·Stoner, M.·Manning, J.·Mushala, B.·Bhattarai, N.·Sharifi-Sanjani, M.·Scott, I.
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Abstract

Myocardial infarction remains one of the leading causes of mortality. Reperfusion of the infarcted myocardium restores blood flow and reduces primary ischemic injury. However, despite its protective function, reperfusion is also associated with several deleterious outcomes that can result in ischemia-reperfusion (I/R) injury to cardiac tissue. While negative outcomes such as reactive oxygen species generation are strongly associated with I/R injury, cardiac energy metabolism is also greatly disrupted. Furthermore, previous studies have shown that the restoration of normal fuel oxidation in the myocardium regulates the extent of contractile recovery. A better understanding of the pathophysiological mechanisms underlying I/R injury may allow us to develop new treatments that limit the negative aspects of the process. In this study, we examined the role played by GCN5L1, a protein implicated in the regulation of energy metabolism, in I/R injury. We demonstrate that cardiac-specific loss of GCN5L1 promotes the inhibitory phosphorylation of pyruvate dehydrogenase in vitro and in vivo, a process likely to inhibit glucose oxidation, and that this corresponds to increased myocardial damage following ischemia-reperfusion (I/R) injury.

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Bugga, P., Stoner, M., Manning, J., Mushala, B., Bhattarai, N., Sharifi-Sanjani, M., Scott, I.. 2024-06-03. GCN5L1 regulates glucose and ketone body metabolism during cardiac ischemia-reperfusion injury. https://doi.org/10.1101/2024.06.03.597148

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