The Effect of a Dominant Inhibitory p53 Protein on Stress Responses Induced by Toxic and Non-Toxic Concentrations of

Renáta Schipp1, Judit Varga1, Judit Bátor1

  • 1Department of Medical Biology, Medical School, University of Pécs, 7624 Pécs, Hungary.

Biology
|December 30, 2025
PubMed

Insights

Toxic anisomycin induces apoptosis via p53-dependent pathways, while non-toxic concentrations activate stress responses. Exosomes may mediate the apoptotic signaling in PC12 cells.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Anisomycin inhibits eukaryotic translation and protein synthesis, inducing apoptosis at toxic concentrations.
  • Sublethal anisomycin concentrations activate cellular stress pathways without inhibiting translation.
  • The role of p53 in anisomycin-induced cellular responses requires further investigation.

Purpose of the Study:

  • To compare the signaling effects of toxic and non-toxic anisomycin concentrations in PC12 cells.
  • To investigate the involvement of the p53 tumor suppressor protein in anisomycin-induced apoptosis and stress responses.
  • To explore the potential role of exosomal paracrine signaling in anisomycin-induced apoptosis.

Main Methods:

  • PC12 cells and a p53-inhibited PC12 cell line were treated with toxic (1 µg/mL) and non-toxic (10 ng/mL) anisomycin.
  • Apoptosis-mediating events such as PKR cleavage, eIF2α phosphorylation, and caspase activation were assessed.
  • MAPK pathways (JNK, p38 MAPK, ERK) were analyzed.
  • Exosomal signaling was investigated.

Main Results:

  • High anisomycin concentrations induced apoptosis-mediating events (PKR cleavage, eIF2α phosphorylation, caspase activation) in a p53-dependent manner.
  • Low anisomycin concentrations stimulated MAPK pathways (JNK, p38 MAPK, ERK), with complex p53 involvement.
  • Exosomal paracrine signaling appeared to support the apoptotic response.

Conclusions:

  • Anisomycin's apoptotic effects are concentration-dependent and involve p53.
  • Non-toxic anisomycin activates MAPK signaling pathways, with p53 playing a regulatory role.
  • Exosomes contribute to anisomycin-induced cellular communication and apoptosis.

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