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Poly(ADP-ribose) polymerase regulates glycolytic activity in kidney proximal tubule epithelial cells

Hana Song1, Sang Pil Yoon2, Jinu Kim3

  • 1Department of Biomedicine and Drug Development, Jeju National University, Jeju, Korea.

Anatomy & Cell Biology
|July 7, 2016
PubMed

Insights

Poly(ADP-ribose) polymerase (PARP) activation inhibits kidney cell glycolysis. Inhibiting PARP enhances glucose metabolism and glycolytic enzyme activity in proximal tubule cells, suggesting a role in renal injury.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Renal injury selectively damages proximal tubules by inhibiting glycolysis.
  • The molecular mechanisms underlying this damage are not fully understood.
  • Poly(ADP-ribose) polymerase (PARP) activation is implicated in proximal tubular cell death in renal disorders.

Purpose of the Study:

  • To investigate the role of PARP in regulating glycolytic flux in kidney proximal tubule epithelial cells.
  • To determine if PARP inhibition affects glucose metabolism and glycolytic enzyme activity.

Main Methods:

  • Utilized LLC-PK1 pig kidney proximal tubule epithelial cells.
  • Employed XFp extracellular flux analysis to measure glycolytic flux.
  • Assessed the impact of glucose incubation and PARP inhibition using 3-aminobenzamide (3-AB).

Main Results:

  • Glucose increased PARP activation and the activity of key glycolytic enzymes.
  • PARP inhibition by 3-AB dose-dependently prevented glucose-induced PARP activation.
  • PARP inhibition significantly enhanced glucose-mediated increases in extracellular acidification rate and augmented specific glycolytic enzyme activities.

Conclusions:

  • PARP activation appears to regulate glycolytic activity in kidney proximal tubule cells.
  • PARP may exert its regulatory role through poly(ADP-ribosyl)ation of hexokinase, phosphofructokinase-1, and glyceraldehyde-3-phosphate dehydrogenase.
  • These findings suggest a novel mechanism by which PARP contributes to proximal tubule dysfunction after renal injury.
Keywords:
Glyceraldehyde-3-phosphate dehydrogenaseGlycolysisHexokinaseKidney proximal tubulesPhosphofructokinase-1Poly(ADP-ribose) polymerases

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