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Updated: Jul 27, 2026

Monitoring Stub1-Mediated Pexophagy
Published on: May 12, 2023
Peroxisome proliferator-activated receptor delta is a specific sensor for teratogenic valproic acid derivatives
1Zentrumsabteilung für Lebensmitteltoxikologie, Tierärztliche Hochschule Hannover, Bischofsholer Damm 15/115, D-30173, Hannover, Germany. Alfonso.Lampen@tiho-hannover.de
Abstract:
The antiepileptic drug valproic acid (2-propylpentanoic acid) is a potent teratogen in both humans and mice. Valproic acid can induce differentiation of F9 teratocarcinoma cells and stimulate peroxisome proliferator-activated receptor (PPAR) activity. In this study, the structure-activity relationship between valproic acid, its teratogenic and non-teratogenic analogues (branched small- and medium chain fatty acids) and the three PPAR subtypes alpha, gamma or delta was investigated. PPAR-alpha and PPAR-gamma were activated by some valproic acid-derivatives; however, no correlation between teratogenicity and receptor activation could be observed. In contrast, only valproic acid and exclusively its teratogenic analogues were able to activate PPAR-delta in different cellular systems. However, valproic acid appears not to be a direct ligand of PPAR-delta, since in contrast to carbaprostacyclin (cPGI), valproic acid showed not to be able to induce complex formation of PPAR-delta-retinoid X receptor (RXR) heterodimers on DNA. In conclusion, in contrast to PPAR-alpha and PPAR-gamma, PPAR-delta shows to be a specific sensor for teratogenic valproic acid-derivatives.
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