TY - JOUR
T1 - New insights in the targets of action of dimethyl fumarate in endothelial cells
T2 - effects on energetic metabolism and serine synthesis in vitro and in vivo
AU - Ocaña, Mª ªC
AU - Bernal, Manuel
AU - Yang, Chendong
AU - Caro, Carlos
AU - Domínguez, Alejandro
AU - Vu, Hieu S.
AU - Cárdenas, Casimiro
AU - García-Martín, María Luisa
AU - DeBerardinis, Ralph J.
AU - Quesada, Ana R.
AU - Martínez-Poveda, Beatriz
AU - Medina, Miguel Ángel
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - Dimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. This drug is approved and currently used for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity was reported some years ago. Due to the current clinical relevance of this compound and the recently manifested importance of endothelial cell metabolism on the angiogenic switch, we wanted to elucidate whether dimethyl fumarate has an effect on energetic metabolism of endothelial cells. Different experimental approximations were performed in endothelial cells, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration in endothelial cells, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in these cells. Dimethyl fumarate alters the energetic metabolism of endothelial cells in vitro and in vivo through an unknown mechanism, which could be the cause or the consequence of its pharmacological activity. This new discovery on the targets of this compound could open a new field of study regarding the mechanism of action of dimethyl fumarate.
AB - Dimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. This drug is approved and currently used for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity was reported some years ago. Due to the current clinical relevance of this compound and the recently manifested importance of endothelial cell metabolism on the angiogenic switch, we wanted to elucidate whether dimethyl fumarate has an effect on energetic metabolism of endothelial cells. Different experimental approximations were performed in endothelial cells, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration in endothelial cells, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in these cells. Dimethyl fumarate alters the energetic metabolism of endothelial cells in vitro and in vivo through an unknown mechanism, which could be the cause or the consequence of its pharmacological activity. This new discovery on the targets of this compound could open a new field of study regarding the mechanism of action of dimethyl fumarate.
UR - http://www.scopus.com/inward/record.url?scp=85174954304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85174954304&partnerID=8YFLogxK
U2 - 10.1038/s42003-023-05443-4
DO - 10.1038/s42003-023-05443-4
M3 - Article
C2 - 37880317
AN - SCOPUS:85174954304
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 1084
ER -