Caloric restriction induces H(2)O(2) formation as a trigger of AMPK-eNOS-NO pathway in obese rats: role for CAMKII

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Item Type:	Article
Title:	Caloric restriction induces H(2)O(2) formation as a trigger of AMPK-eNOS-NO pathway in obese rats: role for CAMKII
Creators Name:	García-Prieto, C.F., Gil-Ortega, M., Plaza, A., Manzano-Lista, F.J., González-Blázquez, R., Alcalá, M., Rodríguez-Rodríguez, P., Viana, M., Aranguez, I., Gollasch, M., Somoza, B. and Fernández-Alfonso, M.S.
Abstract:	Caloric restriction (CR) improves endothelial function through the upregulation of adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Moreover, hydrogen peroxide (H(2)O(2)) is upregulated in yeast subjected to CR. Our aim was to assess if mild short-term CR increases vascular H(2)O(2) 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 H(2)O(2) in aortic rings (H2O2 levels (fa/faAL)=0.5 ± 0.05 nmol/mg vs. H(2)O(2) 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-dD-glucose induced a significant increase in: i) superoxide anion and H(2)O(2) 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 Ca(2+)/calmodulin-dependent kinase II (CamkII) silencing. In conclusion, we propose that mild short-term CR might be a trigger of mechanisms aimed at protecting the vascular wall by the increase of H(2)O(2), which then activates AMPK and nitric oxide release, thus improving endothelium-dependent relaxation. In addition, we demonstrate that CAMKII play a key role in mediating CR-induced AMPK activation through H(2)O(2) increase.
Keywords:	Caloric Restriction, Endothelial Function, Obesity, H(2)O(2), AMPK, Animals, Rats
Source:	Free Radical Biology and Medicine
ISSN:	0891-5849
Publisher:	Elsevier
Volume:	139
Page Range:	35-45
Date:	1 August 2019
Official Publication:	https://doi.org/10.1016/j.freeradbiomed.2019.05.016
PubMed:	View item in PubMed

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