α-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population

Abstract

We present here the data showing, in standard cultures exposed to atmospheric O 2 concentration, that alpha-tocopherol acetate (α-TOA) has a positive impact on primitive cells inside mesenchymal stromal cell (MstroC) population, by maintaining their proliferative capacity. α-TOA decreases the O 2 consumption rate of MStroC probably by impacting respiratory chain complex II activity. This action, however, is not associated with a compensatory increase in glycolysis activity, in spite of the fact that the degradation of HIF-1α was decreased in presence of α-TOA. This is in line with a moderate enhancement of mtROS upon α-TOA treatment. However, the absence of glycolysis stimulation implies the inactivity of HIF-1α which might -if it were active -be related to the maintenance of stemness. It should be stressed that α-TOA might act directly on the gene expression as well as the mtROS themselves, which remains to be elucidated.

α-Tocopherol Attenuates Oxidative Phosphorylation of CD34+ Cells, Enhances Their G0 Phase Fraction and Promotes Hematopoietic Stem and Primitive Progenitor Cell Maintenance

“…The improved maintenance of HSC was seen concerning the effects of αTOA on MSCs [3] whose mitochondrial respiration was impacted, similarly to the results of our study. However, all other effects were different in comparison to those evidenced in CD34 + cells, i.e., αTOA did not impact MSC cycling and did not have an effect on HIF-2, but it did stabilize HIF-1α, which seems to be related to the ROS increase detected at 24 h after αTOA treatment.…”

“…As a matter of fact, the culture that was not supplemented with αTOA should be considered rather as a vitamin E deficiency model [3]. Indeed, our proteomic analysis (data not shown) confirms a high activity of adipocyte plasma membrane associated protein (APMAP), exhibiting a high arylesterase activity, as well as seven enzymes of the mevalonate pathway (whose precursor is acetate).…”

“…As an injectable drug, this molecule is usable in ex vivo cultures and is very appropriate for clinical grade cell engineering. In our previous work with mesenchymal stromal cells [3], we discovered an interesting action of αTOA ex vivo: it decreases the mitochondrial Biomolecules 2021, 11, 558 2 of 18 oxygen consumption rate (OCR) and increases mitochondrial reactive oxygen species ROS without affecting glycolysis. Furthermore, αTOA in parallel enhances maintenance of the proliferative capacity and primitiveness of multipotent mesenchymal stem cells without affecting proliferation itself.…”