Modulation of proteasome activity by vitamin E in THP-1 monocytes.
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.
Munteanu
Adelina
A
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Ricciarelli
Roberta
R
Massone
Sara
S
Zingg
Jean-Marc
JM
D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D019438:Ritonavir / Q000494:pharmacology; D024505:Tocopherols / Q000494:pharmacology; D024508:Tocotrienols / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D007976:Leupeptins; D011480:Protease Inhibitors; C495901:TP53 protein, human; D024508:Tocotrienols; D016159:Tumor Suppressor Protein p53; C063261:acetylleucyl-leucyl-norleucinal; D014810:Vitamin E; D050760:Cyclin-Dependent Kinase Inhibitor p27; C002744:3-nitrotyrosine; D014443:Tyrosine; D046988:Proteasome Endopeptidase Complex; D019438:Ritonavir; D024505:Tocopherols