RT Journal Article
T1 Inactivation of Foxo3a and subsequent downregulation of PGC-1 alpha mediate nitric oxide-induced endothelial cell migration
A1 Borniquel, Sara
A1 García Quintáns, Nieves
A1 Valle, Inmaculada
A1 Olmos Buchelt, Yolanda
A1 Wild, Brigitte
A1 Martínez Granero, Francisco
A1 Soria, Estrella
A1 Lamas, Santiago
A1 Monsalve, María
AB In damaged or proliferating endothelium, production of nitric oxide (NO) from endothelial nitric oxide synthase (eNOS) is associated with elevated levels of reactive oxygen species (ROS), which are necessary for endothelial migration. We aimed to elucidate the mechanism that mediates NO induction of endothelial migration. NO downregulates expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha), which positively modulates several genes involved in ROS detoxification. We tested whether NO-induced cell migration requires PGC-1 alpha downregulation and investigated the regulatory pathway involved. PGC-1 alpha negatively regulated NO-dependent endothelial cell migration in vitro, and inactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is activated by NO, reduced NO-mediated downregulation of PGC-1 alpha. Expression of constitutively active Foxo3a, a target for Akt-mediated inactivation, reduced NO-dependent PGC-1 alpha downregulation. Foxo3a is also a direct transcriptional regulator of PGC-1 alpha, and we found that a functional FoxO binding site in the PGC-1 alpha promoter is also a NO response element. These results show that NO-mediated downregulation of PGC-1 alpha is necessary for NO-induced endothelial migration and that NO/protein kinase G (PKG)-dependent downregulation of PGC-1 alpha and the ROS detoxification system in endothelial cells are mediated by the PI3K/Akt signaling pathway and subsequent inactivation of the FoxO transcription factor Foxo3a.
PB Taylor and Francis
SN 0270-7306
YR 2010
FD 2010-08
LK https://hdl.handle.net/20.500.14352/105407
UL https://hdl.handle.net/20.500.14352/105407
LA eng
NO Borniquel S, García-Quintáns N, Valle I, Olmos Y, Wild B, Martínez-Granero F, Soria E, Lamas S, Monsalve M. Inactivation of Foxo3a and Subsequent Downregulation of PGC-1α Mediate Nitric Oxide-Induced Endothelial Cell Migration. Molecular and Cellular Biology. 2010;30(16):4035-44.
NO Ministerio de Ciencia e Innovación (España)
NO Sociedad Española de Nefrología
NO Centro Nacional de Investigaciones Cardiovasculares
NO Bancaja
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 29 abr 2025