Excessive Oxidative Stress Contributes to Increased Acute ER Stress Kidney Injury in Aged Mice

Oxidative Medicine and Cellular Longevity
Xiaoyan LiuFeng Zheng

Abstract

The aged kidney is susceptible to acute injury due presumably to its decreased ability to handle additional challenges, such as endoplasmic reticulum (ER) stress. This was tested by giving tunicamycin, an ER stress inducer, to either old or young mice. Injection of high dose caused renal failure in old mice, not in young mice. Moreover, injection of low dose resulted in severe renal damage in old mice, confirming the increased susceptibility of aged kidney to ER stress. There existed an abnormality in ER stress response kinetics in aged kidney, characterized by a loss of XBP-1 splicing and decreased PERK-eIF2α phosphorylation at late time point. The presence of excessive oxidative stress in aged kidney may play a role since high levels of oxidation increased ER stress-induced cell death and decreased IRE1 levels and XBP-1 splicing. Importantly, treatment with antioxidants protected old mice from kidney injury and normalized IRE1 and XBP-1 responses. Furthermore, older mice (6 months old) transgenic with antioxidative stress AGER1 were protected from ER stress-induced kidney injury. In conclusion, the decreased ability to handle ER stress, partly due to the presence of excessive oxidative stress, may contribute to increased susc...Continue Reading

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Citations

Jul 5, 2019·British Journal of Pharmacology·Francesco VisioliJoao Tomé-Carneiro
Jul 25, 2019·Frontiers in Pharmacology·Alfonso Rubio-NavarroJuan Antonio Moreno
Jan 13, 2021·Biomolecules·Elizabeth Figueroa-JuárezClaudia Tovar-Palacio

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BETA
transgenic
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PCR
ELISA
electron microscopy
light
MDA

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Meta Imaging

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