α-Tocopherol Transfer Protein (α-TTP) sequesters α-tocopherol out of eight naturally occurring Vitamin E isomers in man . The reasons for the preferential α-tocopherol homeostasis over the similarly abundant γ-tocopherol isomer are currently not known.
In this work, we describe the engineering of a biophysically functional TTP variant with its vitamer selectivity shifted towards γ-tocopherol . Using primary human umbilical vein cells (HUVEC) it is shown that α-TTP significantly reduces cytokine-induced mRNA expression of the pro-inflammatory cytokines IL6, CCL2, TNF and ICAM1 while γ-TTP is not able to attenuate cytokine-mediated transcription. The observed differences indicate that cytokine suppression occurs primarily in the presence of α-tocopherol and also provide clues on the preferential homeostasis of the later in man.
This work was carried out in the group of Prof. Achim Stocker.
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