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Modulation of proteasome activity by vitamin E in THP‐1 monocytes
Author(s) -
Munteanu Adelina,
Ricciarelli Roberta,
Massone Sara,
Zingg JeanMarc
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1103.5
Subject(s) - oxidative stress , ritonavir , proteasome , cd36 , glutathione , chemistry , pharmacology , antioxidant , biochemistry , vitamin e , biology , enzyme , receptor , immunology , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy
The anti‐retroviral protease inhibitor, ritonavir, stimulates CD36 scavenger receptor expression in THP‐1 monocytes, an event that is prevented by α‐tocopherol co‐treatment. Ritonavir furthermore leads to cellular proteasome inhibition, increasing the level of oxidative stress in these cells. Since α‐tocopherol can reduce oxidative stress, it appears likely that normalization of CD36 over‐expression is a consequence of scavenging free radicals produced after proteasome inhibition by ritonavir. Indeed, the proteasome inhibitor, ALLN, produced levels of oxidative stress similar to those induced by ritonavir; however, α‐tocopherol was able to reverse only the effect of ritonavir, and not that of ALLN. Accordingly, α‐tocopherol could normalize the amounts of 3‐nitrotyrosine‐modified proteins only after ritonavir treatment. In the absence of any proteasome inhibitor, intrinsic cellular proteasome activity was not modulated by α‐tocopherol; however, some natural vitamin E analogues and synthetic derivatives could significantly inhibit cellular proteasome activity. Because in our experimental system oxidative stress is reduced by α‐tocopherol only when the proteasome is inhibited by ritonavir and not by ALLN, it is concluded that α‐tocopherol normalizes proteasome activity through a mechanism that does not involve the antioxidant property of the vitamin.