Aldosterone Induces DNA Damage and Activation of Nrf2 Mainly in Tubuli of Mouse Kidneys

Autor: Ronja Balhorn, Christina Hartmann, Nicole Schupp
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
distal tubuli
NF-E2-Related Factor 2
medicine.drug_class
DNA damage
030232 urology & nephrology
Renal function
Blood Pressure
Lipocalin
Kidney
Article
Nrf2
Catalysis
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Internal medicine
medicine
Animals
Renal Insufficiency
Chronic
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
aldosterone
Aldosterone
Organic Chemistry
General Medicine
medicine.disease
kidney damage
Computer Science Applications
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Mineralocorticoid
chronic kidney disease
DNA Damage
Kidney disease
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 13
International Journal of Molecular Sciences, Vol 21, Iss 4679, p 4679 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21134679
Popis: Hypertensive patients have an increased risk of developing chronic kidney disease (CKD). Many of these patients have increased levels of the blood pressure regulating mineralocorticoid aldosterone. As a protection against aldosterone-induced damage, kidney cells can upregulate key regulators of the antioxidant defense, such as nuclear factor-erythroid-2-related factor 2 (Nrf2). In the present study aldosterone-induced kidney damage and Nrf2 activation in kidney cells of mice treated with three different concentrations of aldosterone for 4 weeks was localized. Increased albumin and neutrophil gelatinase-associated lipocalin (NGAL) in urine revealed an impaired kidney function of the aldosterone-infused mice. Localization of aldosterone-induced oxidative damage (in the form of DNA lesions) in specific kidney cells showed an increase in proximal tubuli and to an even greater extend in distal tubuli. Phosphorylated Nrf2 was increased in distal tubule cells after aldosterone-infusion. Nrf2 activation in proximal tubuli or in glomeruli after aldosterone-treatment could not be observed. Nrf2 target genes and proteins analyzed, paradoxically, showed a downregulation in the whole kidney. Aldosterone-treated mice exhibited an increased kidney injury and DNA damage in distal and proximal tubuli. Nrf2 seemed only to be specifically activated in distal tubule cells, where we also detected the highest amount of oxidative damage.
Databáze: OpenAIRE
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