Young and Especially Senescent Endothelial Microvesicles Produce NADPH: The Fuel for Their Antioxidant Machinery

Oxidative Medicine and Cellular Longevity
Guillermo BodegaManuel R Ramírez

Abstract

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 react...Continue Reading

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Citations

Oct 3, 2019·Journal of Cellular and Molecular Medicine·Zeyu ShuQiang Zhang
Nov 17, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sixian YouStephen A Boppart
Jul 2, 2019·Journal of Extracellular Vesicles·G BodegaR M Ramírez
Nov 16, 2020·Microvascular Research·Cheng YuanXiaoyan Wu
Oct 28, 2020·Biological Chemistry·Inken LorenzenEva-Maria Hanschmann
Mar 21, 2021·Free Radical Biology & Medicine·Changhai TianIrving H Zucker
Mar 21, 2021·Cancer Research·Sixian YouStephen A Boppart
May 6, 2021·Free Radical Biology & Medicine·Nan YangMing-Lin Liu
Apr 17, 2021·Proteomics·Bethany ClaridgeDavid W Greening
Oct 6, 2021·Journal of Extracellular Vesicles·Yujia YinXipeng Wang

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Methods Mentioned

BETA
Flow Cytometry
Protein Assay
confocal microscopy

Software Mentioned

CXP
IDA
Analyst TF
Mascot Server
Analyst® TF
Matrix Science
Image J

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