RT Journal Article
T1 Caloric restriction induces H2O2 formation as a trigger of AMPK-eNOS-NO pathway in obese rats: Role for CAMKII.
A1 García Prieto, Concha
A1 Gil Ortega, Marta
A1 Plaza, Adrián
A1 González Blázquez, Raquel
A1 Alcalá, Martín
A1 Rodríguez Rodríguez, Pilar
A1 Viana, Marta
A1 Aránguez Alonso, María Isabel
A1 Gollasch, Maik
A1 Somoza, Beatriz
A1 Manzano Lista, Francisco Javier
A1 Fernández Alfonso, María Soledad
AB Caloric restriction (CR) improves endothelial function through the upregulation of adenosine monophosphateactivated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Moreover, hydrogen peroxide (H2O2) is upregulated in yeast subjected to CR. Our aim was to assess if mild short-term CR increases vascular H2O2 formation as a link with AMPK and eNOS activation. Twelve-week old Zucker obese (fa/fa) and control Zucker lean male rats were fed a standard chow either ad libitum (AL, n=10) or with a 20% CR (CR, n=10) for two weeks. CR significantly improved relaxation to ACh in fa/fa rats because of an enhanced endogenous production of H2O2 in aortic rings (H2O2 levels fa/ faAL=0.5 ± 0.05 nmol/mg vs. H2O2 levels fa/faCR=0.76 ± 0.07 nmol/mg protein; p<0.05). Expression of mitochondrial superoxide dismutase (Mn-SOD) and total SOD activity were increased in aorta from fa/fa animals after CR. In cultured aortic endothelial cells, serum deprivation or 2-deoxy-D-glucose induced a significant increase in: i) superoxide anion and H2O2 levels, ii) p-AMPK/AMPK and p-eNOS/eNOS expression and iii) nitric oxide levels. This effect was reduced by catalase and strongly inhibited by Ca2+/calmodulin-dependent kinase II (CamkII) silencing. In conclusion, we propose that mild short-term CR might be a trigger of mechanisms aimed at protecting thevascular wall by the increase of H2O2, which then activates AMPK and nitric oxide release, thus improving endothelium-dependent relaxation. In addition, we demonstrate that CAMKII plays a key role in mediating CRinduced AMPK activation through H2O2 increase.
SN 0891-5849
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/93774
UL https://hdl.handle.net/20.500.14352/93774
LA eng
NO García-Prieto CF, Gil-Ortega M, Plaza A, Manzano-Lista FJ, González-Blázquez R, Alcalá M, et al. Caloric restriction induces H2O2 formation as a trigger of AMPK-eNOS-NO pathway in obese rats: Role for CAMKII. Free Radical Biology and Medicine 2019;139:35–45. https://doi.org/10.1016/j.freeradbiomed.2019.05.016.
NO Ministerio de Economía, Comercio y Empresa (España)
NO Fundación Universitaria CEU-San Pablo
NO Univerisdad Complutense de Madrid
NO Fundación Mutua Madrileña
NO Fundación Eugenio Rodríguez Pascual
NO Deutsche Forschungsgemeinschaft
NO Ministerio de Educación, Formación Profesional y Deportes (España)
NO Ministerio de Ciencia, Innovación y Universidades (España)
DS Docta Complutense
RD 5 abr 2025