Modulation of proteasome activity by vitamin E in THP-1 monocytes
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Updated: Jul 9, 2026

Electroporation-Based CRISPR-Cas9-Mediated Gene Knockout in THP-1 Cells and Single-Cell Clone Isolation
Published on: February 28, 2025
Adelina Munteanu1, Roberta Ricciarelli, Sara Massone
1Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Abstract:
In THP-1 monocytes, cellular proteasome inhibition by ritonavir or ALLN is associated with increased production of oxidative stress. Both compounds produced comparable amounts of oxidative stress; however, normalization by alpha-tocopherol occurred solely after inhibition by ritonavir, and not by ALLN. Similar to that, alpha-tocopherol could normalize the reduced formation of 3-nitrotyrosine-modified proteins only after ritonavir treatment. In the absence of any proteasome inhibitor, intrinsic cellular proteasome activity was not modulated by alpha-, beta-, and gamma-tocopherols; however, delta-tocopherol, alpha-tocotrienol, and alpha-tocopheryl phosphate could significantly inhibit cellular proteasome activity and increased the level of p27(Kip1) and p53. Since oxidative stress was reduced by alpha-tocopherol only after proteasome inhibition by ritonavir and not by ALLN, it is concluded that, in this experimental system, alpha-tocopherol does not act as an antioxidant but interferes with the inhibitory effect of ritonavir.
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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