Affiliation:
1. Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China; and
2. University of Wyoming College of Health Sciences, Laramie, Wyoming
Abstract
Hypoxia-inducible factor (HIF)-1α is a key regulator of anaerobic energy metabolism. We asked the following question: Does the breakdown of microtubular structures influence glycolysis in hypoxic cardiomyocytes by regulating HIF-1α? Neonatal rat cardiomyocytes were cultured under hypoxic conditions, while microtubule-stabilizing (paclitaxel) and -depolymerizing (colchicine) agents were used to change microtubular structure. Models of high microtubule-associated protein 4 (MAP4) expression and RNA interference of microtubulin expression were established. Microtubular structural changes and intracellular HIF-1α protein distribution were observed with laser confocal scanning microscopy. Content of key glycolytic enzymes, viability, and energy content of cardiomyocytes were determined by colorimetry and high-performance liquid chromatography. HIF-1α protein content and mRNA expression were determined by Western blotting and real-time PCR, respectively. Low doses of microtubule-stabilizing agent (10 μmol/l paclitaxel) and enhanced expression of MAP4 stabilized the reticular microtubular structures in hypoxic cardiomyocytes, increased the content of key glycolytic enzymes, ameliorated energy supply and enhanced cell viability, and upregulated HIF-1α protein expression and endonuclear aggregation. In contrast, the microtubule-depolymerizing agent (10 μmol/l colchicine) or reduced microtubulin expression had adverse affects on the same parameters, in particular, HIF-1α protein content and endonuclear aggregation. We conclude that microtubular structural changes influence glycolysis in the early stages of hypoxia in cardiomyocytes by regulating HIF-1α content. Stabilizing microtubular structures increases endonuclear and total HIF-1α expression, content of key glycolytic enzymes, and energy supply. These findings provide potential therapeutic targets for ameliorating cell energy metabolism during early myocardial hypoxia.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
18 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献