Blood pressure has only minor influence on aldosterone-induced oxidative stress and DNA damage in vivo

Queisser, Nina; Amann, Kerstin; Hey, Valentin; Habib, Samy L.; Schupp, Nicole

doi:10.1016/j.freeradbiomed.2012.10.549

Cited by 29 publications

(35 citation statements)

References 54 publications

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“…Nrf2 is able to protect cells from oxidative DNA damage in vivo: Nrf2-deficient, but not wild-type, mice that are exposed to diesel exhaust particles showed increased levels of 8-oxodG in bronchial epithelial cells (1,38), pointing out the importance of Nrf2 in the fight against oxidative DNA damage. Although Nrf2 activation was observed in our animal study, a high amount of DNA damage was found in aldosterone-treated rat kidneys (41), indicating that the response was not strong enough to protect the animals against these effects.…”

Section: Discussioncontrasting

confidence: 65%

“…However, aldosterone also exerts rapid, nongenomic effects, among them being the production of ROS via NADPH oxidase (52). We recently found aldosterone to be genotoxic and to produce oxidative stress at very low concentrations in renal tubule cells (43,49) and in rat kidneys (41). Aldosterone levels are increased in a subgroup of hypertensive patients with prevalence of 8%-13% (13,47) and in patients with resistant hypertension, with a prevalence of 20% (5).…”

Section: Innovationmentioning

confidence: 99%

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Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells both In Vitro and In Vivo

Queisser¹,

Oteiza²,

Hey³

et al. 2013

Free Radical Biology and Medicine

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Section: Discussioncontrasting

confidence: 65%

Section: Innovationmentioning

confidence: 99%

Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells both In Vitro and In Vivo

Queisser¹,

Oteiza²,

Hey³

et al. 2013

Free Radical Biology and Medicine

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“…In agreement with our previous findings and with the roles of ERK1/2 and STAT3 on cell proliferation and survival, Ald caused an increase in cell proliferation both in vitro and in vivo. Increased cell proliferation was previously detected in kidneys from DOCA/salt‐treated rats, mainly in the tubular regions .…”

Section: Discussionsupporting

confidence: 93%

Aldosterone activates the oncogenic signals ERK1/2 and STAT3 via redox‐regulated mechanisms

Queisser

Schupp

Schwarz

et al. 2017

Molecular Carcinogenesis

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Epidemiological studies found an increased risk for kidney cancer in hypertensive patients, of which a subgroup has high aldosterone (Ald) levels. We recently showed that Ald is genotoxic both in kidney tubular cells and in rats with mineralocorticoid-mediated hypertension. The present work investigated in vitro and in vivo, if the oxidative stress-mediated activation of the ERK1/2 pathway, and its downstream target STAT3, could be one mechanism involved in the potential oncogenic capability of excess Ald exposure. The effects of excess Ald were investigated in LLC-PK1 cells and in Ald-induced hypertensive rats. Ald caused cRaf, MEK1/2, and ERK1/2 phosphorylation both in LLC-PK1 cells and in rat kidneys. ERK1/2 activation led to an increased phosphorylation of MSK1, p90RSK, and STAT3. The involvement of ERK1/2 in the activation of STAT3 was evidenced by the capacity of the MEK inhibitor U0126 to prevent Ald-mediated ERK1/2 and STAT3 phosphorylation.Both in vitro and in vivo, the activation of ERK1/2 and STAT3 by Ald was dependent on the mineralocorticoid receptor and was triggered by an increase in cellular oxidants. Ald-mediated oxidant increase was in part due to the activation of the enzymes NADPH oxidase and NO synthase. 1 On the other hand, we recently showed that excess Ald is genotoxic and causes oxidative stress in renal tubular cells 2,3 and in rat kidneys. [4][5][6] In hypertensive patients, epidemiological studies revealed higher cancer mortality and an increased risk to develop kidney cancer. 7-11Proposed underlying factors are the mitogenic effects of the blood pressure-regulating hormones angiotensin II and Ald. Abnormalities in apoptotic and proliferative processes associated with hypertension could lead to cellular overgrowth.

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“…Kidney sections (3 μm thick) were stained with periodic acid-Schiff (PAS), and immunohistochemistry was performed according to an established procedure [13]. Slit pore diameter was measured as previously described [30,32].…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

“…In accordance with another research [10], we have demonstrated that both oxidative stress (OS) [11] and endoplasmic reticulum stress (ERS) [12] are involved in Aldo-induced podocyte injury. OS is characterized by the increased formation of reactive oxygen species (ROS), exceeding the endogenous antioxidant capacity, and DNA oxidative damage [13], whereas ERS is characterized by the increased expression of ERS markers, such as GRP78, CHOP, and so on [14]. Novel therapeutic strategies aimed at attenuating OS and/or ERS may ameliorate Aldo-induced podocyte injury.…”

Section: Introductionmentioning

confidence: 99%

Berberine Improved Aldo-Induced Podocyte Injury via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress Pathways both In Vivo and In Vitro

Wang¹,

Xu²,

He³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Berberine, a naturally occurring isoquinoline alkaloid, acts against oxidative stress (OS) and endoplasmic reticulum stress (ERS), both of which are responsible for Aldosterone (Aldo) -induced podocyte injury. However, the direct effects of berberine on Aldo-induced OS, ERS, and podocyte injury are not well defined. Methods: Uninephrectomized Sprague-Dawley rats were given 1% NaCl (salt) in their water and an Aldo infusion (0.75 µg/h) for 28 days to induce podocyte injury in the Aldo group. In the Aldo/berberine group, in addition to Aldo infusion, rats were administered 150 mg/kg berberine per day by gastric gavage for 4 weeks. Podocytes were incubated in media containing either buffer or Aldo in the presence or absence of berberine for variable time periods. The kidney tissues and podocytes were then investigated using morphological analysis, immunohistochemistry, transmission electron microscopy, western blot, DHE staining, DCFDA fluorescence, and Annexin V staining. Results: Here, we have reported that berberine attenuated Aldo-induced OS, ERS, and podocyte injury both in vivo and in vitro. Additionally, berberine treatment improved the extensive fusion of foot processes in electron micrographs resulting from Aldo/salt infusion in rats. Conclusion: Berberine may be examined as an effective agent against Aldo-induced podocyte injury.

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Blood pressure has only minor influence on aldosterone-induced oxidative stress and DNA damage in vivo

Cited by 29 publications

References 54 publications

Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells both In Vitro and In Vivo

Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells both In Vitro and In Vivo

Aldosterone activates the oncogenic signals ERK1/2 and STAT3 via redox‐regulated mechanisms

Berberine Improved Aldo-Induced Podocyte Injury via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress Pathways both In Vivo and In Vitro

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