RT Journal Article
T1 The intracellular angiotensin system buffersdeleterious effects of the extracellular paracrine system
A1 Villar Cheda, Begoña
A1 Costa Besada, María Alicia
A1 Valenzuela Limiñana, Rita
A1 Pérez Costas, Emma
A1 Meléndez Ferro, Miguel
A1 Labandeira García, José Luis
K1 Extracellular paracrine
K1 Angiotensin
AB The‘classical’renin–angiotensin system (RAS) is a circulating system that controls blood pressure. Local/paracrine RAS,identified in a variety of tissues, including the brain, is involved in different functions and diseases, and RAS blockers arecommonly used in clinical practice. A third type of RAS (intracellular/intracrine RAS) has been observed in some types of cells,including neurons. However, its role is still unknown. The present results indicate that in brain cells the intracellular RAScounteracts the intracellular superoxide/H2O2and oxidative stress induced by the extracellular/paracrine angiotensin II acting onplasma membrane receptors. Activation of nuclear receptors by intracellular or internalized angiotensin triggers a number ofmechanisms that protect the cell, such as an increase in the levels of protective angiotensin type 2 receptors, intracellularangiotensin, PGC-1αand IGF-1/SIRT1. Interestingly, this protective mechanism is altered in isolated nuclei from brains of agedanimals. The present results indicate that at least in the brain, AT1 receptor blockers acting only on the extracellular or paracrineRAS may offer better protection of cells
PB Nature Publishing Group
SN 2041-4889
YR 2017
FD 2017
LK http://hdl.handle.net/10347/23204
UL http://hdl.handle.net/10347/23204
LA eng
NO Villar-Cheda, B., Costa-Besada, M., Valenzuela, R. et al. The intracellular angiotensin system buffers deleterious effects of the extracellular paracrine system. Cell Death Dis 8, e3044 (2017). https://doi.org/10.1038/cddis.2017.439
NO We thank Dr. Wei-Dong Le for providing the MES 23.5dopaminergic cell line, Dr. Manuel Serrano and Dr. Ruben Nogueiras for providing thetransgenic mice overexpressing SIRT1, and Dr. Daniel Henrion for providing the AT2KO mice. We thank Pilar Aldrey, Iria Novoa and Cristina Gianzo for their technicalassistance. This study was funded by the Spanish Ministry of Economy andCompetitiveness (BFU2015-70523), Spanish Ministry of Health (RD12/0019/0020,RD16/0011/0016 and CIBERNED), Galician Government (XUGA, GRC2014/002ED431G/05 and CIMUS accreditation 2016‐2019) and FEDER (Regional EuropeanDevelopment Fund)
DS Minerva
RD 24 abr 2026