☆ 4.7 Article

Acute detachment of hexokinase II from mitochondria modestly increases oxygen consumption of the intact mouse heart

METABOLISM-CLINICAL AND EXPERIMENTAL (2017)

Journal

METABOLISM-CLINICAL AND EXPERIMENTAL

Volume 72, Issue -, Pages 66-74

Publisher

W B SAUNDERS CO-ELSEVIER INC

DOI: 10.1016/j.metabol.2017.04.008

Keywords

Oxygen consumption; Cardiac metabolism; Hexokinase II; Stable isotopes

Funding

Dutch Heart Foundation [NHS2010B011]

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Abstract

Objective. Cardiac hexokinase II (HKII) can translocate between cytosol and mitochondria and change its cellular expression with pathologies such as ischemia-reperfusion, diabetes and heart failure. The cardiac metabolic consequences of these changes are unknown. Here we measured energy substrate utilization in cytosol and mitochondria using stabile isotopes and oxygen consumption of the intact perfused heart for 1) an acute decrease in mitochondrial HKII (mtHKII), and 2) a chronic decrease in total cellular HKII. Methods/results. We first examined effects of 200 nM TAT (Trans-Activator of Transcription)-HKII peptide treatment, which was previously shown to acutely decrease mtHKII by similar to 30%. In Langendorff-perfused hearts TAT-HKII resulted in a modest, but significant, increased oxygen consumption, while cardiac performance was unchanged. At the metabolic level, there was a nonsignificant (p = 0.076) similar to 40% decrease in glucose contribution to pyruvate and lactate formation through glycolysis and to mitochondrial citrate synthase flux (6.6 +/- 1.1 vs. 11.2 +/- 2.2%), and an 35% increase in tissue pyruvate (27 2 vs, 20 2 pmol/mg; p = 0.033). Secondly, we compared WT and HKII+/- hearts (50% chronic decrease in total HKII). RNA sequencing revealed no differential gene expression between WT and HKII+/- hearts indicating an absence of metabolic reprogramming at the transcriptional level. Langendorff-perfused hearts showed no significant differences in glycolysis (0.34 +/- 0.03 mu mol/min), glucose contribution to citrate synthase flux (35 +/- 2.3%), palmitate contribution to citrate synthase flux (20 +/- 1.1%), oxygen consumption or mechanical performance between WT and HKII+/- hearts. Conclusions. These results indicate that acute albeit not chronic changes in mitochondrial HKII modestly affect cardiac oxygen consumption and energy substrate metabolism. (C) 2017 Elsevier Inc. All rights reserved.

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Identifying the controls on nitrate and metabolic state within the Red River delta (Vietnam) with the use of stable isotopes

Andrew C. Smith, Melanie J. Leng, Suzanne McGowan, Virginia N. Panizzo, Thi Thu Trang Ngo, Thi Nguyet Minh Luu, Ioannis Matiatos, Thu Nga Do, Thi Thao Ta, Anh Duc Trinh

Summary: Anthropogenic activities have caused nitrate pollution and changes in the metabolic state of aquatic ecosystems in the Red River delta, Vietnam. Soil leachate, domestic waste, and agricultural fertilizers were identified as the main sources of nitrate. The delta's geographical location and seasonal changes affect the relative impact of each source. Low dissolved oxygen saturation in the river system is a concern due to high nitrate loads and inputs of organic matter from untreated waste.

JOURNAL OF HYDROLOGY (2024)