Angiotensin II induces oxidative stress and upregulates neuroprotective signaling from the NRF2 and KLF9 pathway in dopaminergic cells
Parga, Juan A. ; Rodriguez-Perez, Ana I. ; Garcia-Garrote, Maria LU
; Rodriguez-Pallares, Jannette
and Labandeira-Garcia, Jose L.
(2018)
In Free Radical Biology and Medicine
129.
p.394-406
- Abstract
Nuclear factor-E2-related factor 2 (NRF2) is a transcription factor that activates the antioxidant cellular defense in response to oxidative stress, leading to neuroprotective effects in Parkinson's disease (PD) models. We have previously shown that Angiotensin II (AngII) induces an increase in reactive oxygen species (ROS) via AngII receptor type 1 and NADPH oxidase (NOX), which may activate the NRF2 pathway. However, controversial data suggest that AngII induces a decrease in NRF2 signaling leading to an increase in oxidative stress. We analyzed the effect of AngII and the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in culture and in vivo, and examined the effects on the expression of NRF2-related genes. Treatment of neuronal... (More)
Nuclear factor-E2-related factor 2 (NRF2) is a transcription factor that activates the antioxidant cellular defense in response to oxidative stress, leading to neuroprotective effects in Parkinson's disease (PD) models. We have previously shown that Angiotensin II (AngII) induces an increase in reactive oxygen species (ROS) via AngII receptor type 1 and NADPH oxidase (NOX), which may activate the NRF2 pathway. However, controversial data suggest that AngII induces a decrease in NRF2 signaling leading to an increase in oxidative stress. We analyzed the effect of AngII and the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in culture and in vivo, and examined the effects on the expression of NRF2-related genes. Treatment of neuronal cell lines Mes23.5, N27 and SH-SY5Y with AngII, 6-OHDA or a combination of both increased ROS production and reduced cell viability. Simultaneously, these treatments induced an increase in expression in the NRF2-regulated genes heme oxygenase 1 (Hmox1), NAD(P)H quinone dehydrogenase 1 (Nqo1) and Kruppel like factor 9 (Klf9). Moreover, overexpression of KLF9 transcription factor caused a reduction in the production of ROS induced by treatment with AngII or 6-OHDA and improved the survival of these neuronal cells. Rats treated with AngII, 6-OHDA or a combination of both also showed an increased expression of NRF2 related genes and KLF9. In conclusion, our data indicate that AngII induces a damaging effect in neuronal cells, but also acts as a signaling molecule to activate NRF2 and KLF9 neuroprotective pathways in cellular and animal models of PD.
(Less)
- author
- Parga, Juan A.
; Rodriguez-Perez, Ana I.
; Garcia-Garrote, Maria
LU
; Rodriguez-Pallares, Jannette
and Labandeira-Garcia, Jose L.
- publishing date
- 2018-12
- type
- Contribution to journal
- publication status
- published
- keywords
- Antioxidant, Heme oxygenase, Neurodegeneration, Parkinson's disease, Redox signaling, Renin-angiotensin system
- in
- Free Radical Biology and Medicine
- volume
- 129
- pages
- 394 - 406
- publisher
- Elsevier
- external identifiers
-
- scopus:85054819686
- pmid:30315936
- ISSN
- 0891-5849
- DOI
- 10.1016/j.freeradbiomed.2018.10.409
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2018 Elsevier Inc.
- id
- 50d07490-1381-4d38-bd5d-2a758da085fd
- date added to LUP
- 2025-01-24 11:54:12
- date last changed
- 2025-05-02 18:52:56
@article{50d07490-1381-4d38-bd5d-2a758da085fd,
abstract = {{<p>Nuclear factor-E2-related factor 2 (NRF2) is a transcription factor that activates the antioxidant cellular defense in response to oxidative stress, leading to neuroprotective effects in Parkinson's disease (PD) models. We have previously shown that Angiotensin II (AngII) induces an increase in reactive oxygen species (ROS) via AngII receptor type 1 and NADPH oxidase (NOX), which may activate the NRF2 pathway. However, controversial data suggest that AngII induces a decrease in NRF2 signaling leading to an increase in oxidative stress. We analyzed the effect of AngII and the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in culture and in vivo, and examined the effects on the expression of NRF2-related genes. Treatment of neuronal cell lines Mes23.5, N27 and SH-SY5Y with AngII, 6-OHDA or a combination of both increased ROS production and reduced cell viability. Simultaneously, these treatments induced an increase in expression in the NRF2-regulated genes heme oxygenase 1 (Hmox1), NAD(P)H quinone dehydrogenase 1 (Nqo1) and Kruppel like factor 9 (Klf9). Moreover, overexpression of KLF9 transcription factor caused a reduction in the production of ROS induced by treatment with AngII or 6-OHDA and improved the survival of these neuronal cells. Rats treated with AngII, 6-OHDA or a combination of both also showed an increased expression of NRF2 related genes and KLF9. In conclusion, our data indicate that AngII induces a damaging effect in neuronal cells, but also acts as a signaling molecule to activate NRF2 and KLF9 neuroprotective pathways in cellular and animal models of PD.</p>}},
author = {{Parga, Juan A. and Rodriguez-Perez, Ana I. and Garcia-Garrote, Maria and Rodriguez-Pallares, Jannette and Labandeira-Garcia, Jose L.}},
issn = {{0891-5849}},
keywords = {{Antioxidant; Heme oxygenase; Neurodegeneration; Parkinson's disease; Redox signaling; Renin-angiotensin system}},
language = {{eng}},
pages = {{394--406}},
publisher = {{Elsevier}},
series = {{Free Radical Biology and Medicine}},
title = {{Angiotensin II induces oxidative stress and upregulates neuroprotective signaling from the NRF2 and KLF9 pathway in dopaminergic cells}},
url = {{http://dx.doi.org/10.1016/j.freeradbiomed.2018.10.409}},
doi = {{10.1016/j.freeradbiomed.2018.10.409}},
volume = {{129}},
year = {{2018}},
}