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

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 α-tocopherol occurred solely after inhibition by ritonavir, and not by ALLN. Similar to that, α-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 α-, β-, and γ-tocopherols; however, δ-tocopherol, α-tocotrienol, and α-tocopheryl phosphate could significantly inhibit cellular proteasome activity and increased the level of p27Kip1 and p53. Since oxidative stress was reduced by α-tocopherol only after proteasome inhibition by ritonavir and not by ALLN, it is concluded that, in this experimental system, α-tocopherol does not act as an antioxidant but interferes with the inhibitory effect of ritonavir. © 2007 IUBMB.