Got glycogen? An energy resource in HIF-mediated prevention of ischemic kidney injury

Volker H Haase1

  • 1Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Kidney International
|March 24, 2020
PubMed

Insights

Pharmacologic inhibition of hypoxia-inducible factor-prolyl hydroxylase domain sensors boosts glycogen synthesis in renal cells. This enhances cellular protection against hypoxia and glucose deprivation, suggesting a role for renal glycogen metabolism in cytoprotection.

Area of Science:

  • Cellular metabolism
  • Renal physiology
  • Hypoxia-inducible factors

Background:

  • Hypoxia-inducible factor (HIF) activation alters glucose metabolism, promoting glycogen storage.
  • Renal cells are susceptible to damage from hypoxia and glucose deprivation.

Purpose of the Study:

  • To investigate the role of hypoxia-inducible factor-prolyl hydroxylase domain (HIF-PHD) inhibition in renal cell metabolism and protection.
  • To determine if enhancing glycogen synthesis via HIF-PHD inhibition confers cytoprotection.

Main Methods:

  • Pharmacologic inhibition of HIF-PHD oxygen sensors in renal epithelial cells.
  • Assessment of glycogen synthesis and cellular response to hypoxia/glucose deprivation.
  • In vivo studies to evaluate cytoprotective effects in a pre-ischemic model.

Main Results:

  • Inhibition of HIF-PHD in renal epithelial cells enhanced glycogen synthesis.
  • Enhanced glycogen synthesis led to protection against subsequent hypoxia and glucose deprivation.
  • In vivo studies supported the role of renal glycogen metabolism in cytoprotection.

Conclusions:

  • Pharmacologic HIF-PHD inhibition can reprogram renal cell metabolism to favor glycogen synthesis.
  • Pre-ischemic HIF-PHD inhibition offers cytoprotection through enhanced renal glycogen metabolism.
  • Renal glycogen metabolism is a key contributor to cellular resilience against ischemic injury.

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