Human Umbilical Vein Endothelial Cells Survive on the Ischemic TCA Cycle under Lethal Ischemic Conditions.

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 101128775 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-3907 (Electronic) Linking ISSN: 15353893 NLM ISO Abbreviation: J Proteome Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, D.C. : American Chemical Society, c2002-
    • Subject Terms:
      Citric Acid Cycle*/physiology ; Human Umbilical Vein Endothelial Cells* ; Ischemia*; Avidin ; Citrate (si)-Synthase ; Coenzyme A ; Humans ; Hypoxia ; Pyruvic Acid ; Tricarboxylic Acids
    • Abstract:
      It is generally believed that vascular endothelial cells (VECs) rely on glycolysis instead of the tricarboxylic acid (TCA) cycle under both normoxic and hypoxic conditions. However, the metabolic pattern of human umbilical vein endothelial cells (HUVECs) under extreme ischemia (hypoxia and nutrient deprivation) needs to be elucidated. We initiated a lethal ischemic model of HUVECs, performed proteomics and bioinformatics, and verified the metabolic pattern shift of HUVECs. Ischemic HUVECs displayed extensive aerobic respiration, including upregulation of the TCA cycle and mitochondrial respiratory chain in mitochondria and downregulation of glycolysis in cytoplasm. The TCA cycle was enhanced while the cell viability was decreased through the citrate synthase pathway when substrates of the TCA cycle (acetate and/or pyruvate) were added and vice versa when inhibitors of the TCA cycle (palmitoyl-CoA and/or avidin) were applied. The inconsistency of the TCA cycle level and cell viability suggested that the extensive TCA cycle can keep cells alive yet generate toxic substances that reduce cell viability. The data revealed that HUVECs depend on "ischemic TCA cycle" instead of glycolysis to keep cells alive under lethal ischemic conditions, but consideration must be given to relieve cell injury.
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    • Contributed Indexing:
      Keywords: citrate synthase; glycolysis; ischemia; tricarboxylic acid cycle; vascular endothelial cells
    • Accession Number:
      0 (Tricarboxylic Acids)
      1405-69-2 (Avidin)
      8558G7RUTR (Pyruvic Acid)
      EC 2.3.3.1 (Citrate (si)-Synthase)
      SAA04E81UX (Coenzyme A)
    • Publication Date:
      Date Created: 20220908 Date Completed: 20221010 Latest Revision: 20221108
    • Publication Date:
      20240829
    • Accession Number:
      PMC9552233
    • Accession Number:
      10.1021/acs.jproteome.2c00255
    • Accession Number:
      36074008