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IGF-1 Signaling Modulates Oxidative Metabolism and Stress Resistance in ARPE-19 Cells Through PKM2 Function

Silvia Ravera1,2, Alessandra Puddu3, Nadia Bertola2

  • 1Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 Genova, Italy.

International Journal of Molecular Sciences
|January 8, 2025
PubMed

Insights

Insulin-like growth factor 1 (IGF-1) alters pyruvate kinase M2 (PKM2) activity in retinal pigment epithelium cells, impacting metabolism and oxidative stress. Klotho may protect against these IGF-1 effects.

Area of Science:

  • Cellular metabolism
  • Retinal biology
  • Molecular signaling

Background:

  • Retinal pigment epithelium (RPE) dysfunction is linked to retinal degenerative diseases.
  • Pyruvate kinase M2 (PKM2) is crucial for cellular metabolism and may be influenced by insulin-like growth factor 1 (IGF-1).

Purpose of the Study:

  • To investigate the impact of IGF-1 on PKM2 in RPE cells.
  • To determine if Klotho can protect RPE cells from IGF-1-induced changes.
  • To explore the role of PKM2 in RPE metabolic and redox balance.

Main Methods:

  • Utilized ARPE-19 cells as an ex vivo model of human pigmented epithelium.
  • Exposed cells to IGF-1 and assessed PKM2 expression, dimerization, and localization.
  • Evaluated cellular energy metabolism and redox balance, with and without Klotho pre-treatment.

Main Results:

  • IGF-1 promoted PKM2 dimerization, reducing its enzymatic activity.
  • This led to altered cellular energy status and decreased oxidative stress.
  • Klotho pre-treatment appeared to counteract the effects of IGF-1.

Conclusions:

  • PKM2 is pivotal in regulating RPE cell metabolism and redox balance.
  • IGF-1's effects on PKM2 may contribute to retinal disease pathogenesis.
  • Klotho shows potential protective effects by modulating IGF-1 signaling and mitochondrial function.
Keywords:
Klothoenergy metabolisminsulin-like growth factor 1isoform M2 of pyruvate kinaseredox balanceretinal pigment epithelium

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