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Young and Especially Senescent Endothelial Microvesicles Produce NADPH: The Fuel
for Their Antioxidant Machinery
#MMPMID29849879
Bodega G
; Alique M
; Bohórquez L
; Morán M
; Magro L
; Puebla L
; Ciordia S
; Mena MC
; Arza E
; Ramírez MR
Oxid Med Cell Longev
2018[]; 2018
(?): 3183794
PMID29849879
show ga
In a previous study, we demonstrated that endothelial microvesicles (eMVs) have a
well-developed enzymatic team involved in reactive oxygen species detoxification.
In the present paper, we demonstrate that eMVs can synthesize the reducing power
(NAD(P)H) that nourishes this enzymatic team, especially those eMVs derived from
senescent human umbilical vein endothelial cells. Moreover, we have demonstrated
that the molecules that nourish the enzymatic machinery involved in NAD(P)H
synthesis are blood plasma metabolites: lactate, pyruvate, glucose, glycerol, and
branched-chain amino acids. Drastic biochemical changes are observed in senescent
eMVs to optimize the synthesis of reducing power. Mitochondrial activity is
diminished and the glycolytic pathway is modified to increase the activity of the
pentose phosphate pathway. Different dehydrogenases involved in NADPH synthesis
are also increased. Functional experiments have demonstrated that eMVs can
synthesize NADPH. In addition, the existence of NADPH in eMVs was confirmed by
mass spectrometry. Multiphoton confocal microscopy images corroborate the
synthesis of reducing power in eMVs. In conclusion, our present and previous
results demonstrate that eMVs can act as autonomous reactive oxygen species
scavengers: they use blood metabolites to synthesize the NADPH that fuels their
antioxidant machinery. Moreover, senescent eMVs have a stronger reactive oxygen
species scavenging capacity than young eMVs.
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