Oxidative stress and cell senescence combine to cause maximal renal Tubular Epithelial Cell Dysfunction and loss in an in vitro Model of Kidney Disease

Small, David M., Bennett, Nigel C., Roy, Sandrine, Gabrielli, Brian G., Johnson, David W. and Gobe, Glenda C. (2013) Oxidative stress and cell senescence combine to cause maximal renal Tubular Epithelial Cell Dysfunction and loss in an in vitro Model of Kidney Disease. Nephron Experimental Nephrology, 122 3-4: 123-130. doi:10.1159/000350726


Author Small, David M.
Bennett, Nigel C.
Roy, Sandrine
Gabrielli, Brian G.
Johnson, David W.
Gobe, Glenda C.
Title Oxidative stress and cell senescence combine to cause maximal renal Tubular Epithelial Cell Dysfunction and loss in an in vitro Model of Kidney Disease
Journal name Nephron Experimental Nephrology   Check publisher's open access policy
ISSN 1660-2129
1660-8151
Publication date 2013-06
Year available 2013
Sub-type Article (original research)
DOI 10.1159/000350726
Open Access Status
Volume 122
Issue 3-4
Start page 123
End page 130
Total pages 8
Place of publication Basel, Switzerland
Publisher S. Karger AG
Collection year 2014
Language eng
Formatted abstract
Background: The incidence and cost of chronic kidney disease (CKD) are increasing. Renal tubular epithelial cell dysfunction and attrition, involving increased apoptosis and cell senescence, are central to the pathogenesis of CKD. The aim here was to use an in vitro model to investigate the separate and cumulative effects of oxidative stress, mitochondrial dysfunction and cell senescence in promoting loss of renal mass.

Methods:
Human kidney tubular epithelial cells (HK2) were treated with moderate hydrogen peroxide (H2O2) for oxidative stress, with or without cell cycle inhibition (apigenin, API) for cell senescence. Adenosine triphosphate (ATP) and oxidative stress were measured by ATP assay, lipid peroxidation, total antioxidant capacity, mitochondrial function with confocal microscopy, MitoTracker Red CMXRos and live cell imaging with JC-1. In parallel, cell death and injury (i.e. apoptosis and Bax/Bcl-XL expression, lactate dehydrogenase), cell senescence (SA-β-galactosidase) and renal regenerative ability (cell proliferation), and their modulation with the anti-oxidant N-acetyl-cysteine (NAC) were investigated.

Results: H2O2 and API, separately, increased oxidative stress and mitochondrial dysfunction, apoptosis and cell senescence. Although API caused cell senescence, it also induced oxidative stress at levels similar to H2O2 treatment alone, indicating that senescence and oxidative stress may be intrinsically linked. When H2O2 and API were delivered concurrently, their detrimental effects on renal cell loss were compounded. The antioxidant NAC attenuated apoptosis and senescence, and restored regenerative potential to the kidney.

Conclusion: Oxidative stress and cell senescence both cause mitochondrial destabilization and cell loss and contribute to the development of the cellular characteristics of CKD.
Keyword Chronic kidney disease
Cell senescence
Oxidative stress
Apoptosis
Mitochondria
Molecular Targets
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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