Modulation of proteasome activity by vitamin E in THP-1 monocytes

Adelina Munteanu1, Roberta Ricciarelli, Sara Massone

  • 1Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.

IUBMB Life
|December 19, 2007
PubMed

Insights

Alpha-tocopherol mitigates oxidative stress and 3-nitrotyrosine formation induced by ritonavir, but not ALLN, in THP-1 monocytes. This suggests alpha-tocopherol interferes with ritonavir

Area of Science:

  • Cellular biology
  • Biochemistry
  • Pharmacology

Background:

  • Proteasome inhibition is linked to oxidative stress.
  • Alpha-tocopherol's role in modulating proteasome activity and oxidative stress requires clarification.

Purpose of the Study:

  • To investigate the effect of proteasome inhibitors ritonavir and ALLN on oxidative stress in THP-1 monocytes.
  • To determine the influence of alpha-tocopherol on proteasome activity and oxidative stress markers under different inhibition conditions.
  • To explore the potential antioxidant or interfering role of alpha-tocopherol.

Main Methods:

  • THP-1 monocytes were treated with ritonavir or ALLN, with or without alpha-tocopherol.
  • Oxidative stress and 3-nitrotyrosine-modified proteins were measured.
  • Cellular proteasome activity was assessed in the presence of various tocopherol derivatives and tocotrienols.

Main Results:

  • Both ritonavir and ALLN increased oxidative stress, but only ritonavir-induced stress was normalized by alpha-tocopherol.
  • Alpha-tocopherol normalized 3-nitrotyrosine formation only after ritonavir treatment.
  • Certain tocopherol derivatives (delta-tocopherol, alpha-tocotrienol, alpha-tocopheryl phosphate) inhibited proteasome activity and increased p27(Kip1) and p53 levels.

Conclusions:

  • Alpha-tocopherol does not act as a direct antioxidant in this system.
  • Alpha-tocopherol interferes with the inhibitory effects of ritonavir on cellular proteasome activity.
  • Specific tocopherol forms can modulate proteasome activity independently of oxidative stress.

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