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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
Summary
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 epitheliumMore Related Videos
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