α‐Tocopherol enhances degranulation in RBL‐2H3 mast cells

Abstract

Based on the observation that 3 months alpha-tocopherol supplementation caused an up-regulation of the mRNA of vesicular transport proteins in livers of mice, the functional relevance was investigated in RBL-2H3 cells, a model for mast cell degranulation. In total, 24 h incubation with 100 muM alpha-tocopherol enhanced the basal and phorbol-12-myristyl-13-acetate/ionomycin-stimulated release of beta-hexosaminidase and cathepsin D as measured by enzymatic analysis as well as Western blotting and immunocytochemistry, respectively. beta-Tocopherol exerted the same effect, whereas alpha-tocopheryl phosphate and trolox were inactive, indicating that both the side chain and the 6-OH group at the chroman ring are essential for activation of degranulation. alpha-Tocopherol did not induce mRNA expression of soluble NSF-attachment protein receptor (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins, such as N-ethylmaleimide sensitive fusion protein, complexin-2, SNAP23 or syntaxin-3, in the RBL-2H3 cell model. In view of the well known alpha-tocopherol-mediated activation of protein phosphatases, which regulate soluble NSF-attachment protein receptor activities by dephosphorylation, underlying mechanisms are discussed in terms of preventing oxidative inactivation of protein phosphatases and so far unknown functions in certain membrane domains.

δ-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders

“…This effect of ␣-T was not mediated by an up-regulation of genes for proteins involved in vesicular transport (e.g. Nsf, Cplx2, Snap23, and Stx3) but through the direct interaction of ␣-T with the plasma membrane (47). The pretreatment requirement of ␣-T for these reported pharmacological effects may be explained by the time necessary for the incorporation of ␣-T molecules into the plasma membrane and for the subsequent transfer of incorporated ␣-T molecules to other cellular organelles and compartments.…”

“…␣-T, the major vitamin E isoform in human plasma, prevents apoptosis induced by 7-ketocholesterol, one of the cholesterol oxidation products in neuronal cells that is markedly increased in NPC1 disease (46). ␣-T has also been shown to stimulate mast cell degranulation, a secretory form of exocytosis (47). This effect of ␣-T was not mediated by an up-regulation of genes for proteins involved in vesicular transport (e.g.…”

Vitamin E: A vitamin still awaiting the detection of its biological function

“…It is not clear whether α‐tocopherol is part of the rafts themselves, triggers recruitment of proteins/lipids to the membrane or modulates the formation of these microdomains. A first hint for the participation in the modulation of membranes processes comes from the here described finding that α‐ (and also β‐) tocopherol increases vesicle‐associated degranulation from mast cells 23.…”

“…Binding of vitamin E to TAPs has been discussed as a mechanism by which α‐tocopherol is transported to intracellular targets where it modulates lipid‐mediated signaling pathways, such as inhibition of the PI3K pathway or vesicular transports. Contributions relevant to these novel perspectives in this issue are 12, 13, 20, 22, 23.…”

Vitamin E, signalosomes and gene expression in T cells

“…Hence, by influencing this cellular process, vitamin E could also modulate TCR signaling. In this regard, a-and b-tocopherols are known to increase vesicle-associated degranulation in mast cells (Hemmerling et al, 2010).…”