l-Carnitine ameliorates the oxidative stress response to angiotensin II by modulating NADPH oxidase through a reduction in protein kinase c activity and NF-κB translocation to the nucleus.
l-Carnitine (LC) exerts beneficial effects in arterial hypertension due, in part, to its antioxidant capacity. We investigated the signalling pathways involved in the effect of LC on angiotensin II (Ang II)-induced NADPH oxidase activation in NRK-52E cells. Ang II increased the generation of superoxide anion from NADPH oxidase, as well as the amount of hydrogen peroxide and nitrotyrosine. Co-incubation with LC managed to prevent these alterations and also reverted the changes in NADPH oxidase expression triggered by Ang II. Cell signalling studies evidenced that LC did not modify Ang II-induced phosphorylation of Akt, p38 MAPK or ERK1/2. On the other hand, a significant decrease in PKC activity, and inhibition of nuclear factor kappa B (NF-kB) translocation, were attributable to LC incubation. In conclusion, LC counteracts the pro-oxidative response to Ang II by modulating NADPH oxidase enzyme via reducing the activity of PKC and the translocation of NF-kB to the nucleus.
Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, CL Profesor García González 2, 41012 Sevilla, Spain.
Antonio J
AJ
Blanca
Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, CL Profesor García González 2, 41012 Sevilla, Spain.
María V
MV
Ruiz-Armenta
Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, CL Profesor García González 2, 41012 Sevilla, Spain.
Sonia
S
Zambrano
Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, CL Profesor García González 2, 41012 Sevilla, Spain.
José L
JL
Miguel-Carrasco
U.G.C. Nefrología, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain.
Francisco M
FM
González-Roncero
Program of Cardiovascular Sciences, Center for Applied Medical Research, University of Navarra, Avda. Pío XII 55, 31008 Pamplona, Spain.
Ana
A
Fortuño
Departamento de Bioquímica, Facultad de Farmacia, Universidad de Sevilla, CL Profesor García González 2, 41012 Sevilla, Spain.
Elisa
E
Revilla
Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, CL Profesor García González 2, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain. Electronic address: mate@us.es.
Alfonso
A
Mate
Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, CL Profesor García González 2, 41012 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain.
Carmen M
CM
Vázquez
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002331:Carnitine / Q000737:chemistry*; D006973:Hypertension / Q000188:drug therapy*; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000378:metabolism*
D016328:NF-kappa B; D000804:Angiotensin II; D019255:NADPH Oxidases; D011493:Protein Kinase C; D002331:Carnitine
Angiotensin II; Arterial hypertension; NADPH oxidase; NRK-52E; l-Carnitine