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β-Cryptoxanthin Maintains Mitochondrial Function by Promoting NRF2 Nuclear Translocation to Inhibit Oxidative
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Abstract:
The mechanisms of acute kidney injury and chronic kidney disease remain incompletely revealed, and drug development is a pressing clinical challenge. Oxidative stress-induced cellular senescence and mitochondrial damage are important biological events in a variety of kidney diseases. As a type of carotenoid, β-Cryptoxanthin (BCX) has various biological functions, which means it is a potential therapeutic candidate for the treatment of kidney disease. However, the role of BCX in the kidney is unclear, and the effect of BCX on oxidative stress and cellular senescence in renal cells is also unknown. Therefore, we conducted a series of studies on human renal tubular epithelial (HK-2) cells in vitro. In the present study, we investigated the effect of BCX pretreatment on H2O2-induced oxidative stress and cellular senescence and explored the potential mechanism of BCX action. The results showed that BCX attenuated H2O2-induced oxidative stress and cellular senescence in HK-2 cells. Moreover, BCX promoted NRF2 nuclear expression, maintained mitochondrial function, and reduced mitochondrial damage in HK-2 cells. In addition, silencing NRF2 altered the protective effect of BCX on mitochondria and significantly reversed the anti-oxidative stress and anti-senescence effects of BCX in HK-2 cells. We concluded that BCX maintained mitochondrial function by promoting NRF2 nuclear translocation to inhibit oxidative stress-induced senescence in HK-2 cells. In light of these findings, the application of BCX might be a promising strategy for the prevention and treatment of kidney diseases.
Insights
Beta-cryptoxanthin (BCX) protects kidney cells from oxidative stress and senescence by maintaining mitochondrial function via the NRF2 pathway. This suggests BCX could be a therapeutic agent for kidney disease.
Area of Science:
- Nephrology
- Cell Biology
- Oxidative Stress Research
Background:
- Kidney disease mechanisms are not fully understood, with oxidative stress and mitochondrial damage contributing to cellular senescence.
- Drug development for kidney diseases is challenging, highlighting the need for novel therapeutic candidates.
- Beta-cryptoxanthin (BCX), a carotenoid, shows potential but its role in kidney health is unexplored.
Purpose of the Study:
- To investigate the protective effects of BCX against oxidative stress and cellular senescence in human renal tubular epithelial (HK-2) cells.
- To elucidate the underlying mechanism of BCX action, focusing on mitochondrial function and the NRF2 pathway.
Main Methods:
- In vitro studies using HK-2 cells exposed to hydrogen peroxide (H2O2) to induce oxidative stress and senescence.
- Pretreatment with BCX and assessment of oxidative stress markers, senescence indicators, and mitochondrial function.
- NRF2 pathway activation and mitochondrial integrity were evaluated, including experiments with NRF2 gene silencing.
Main Results:
- BCX pretreatment significantly attenuated H2O2-induced oxidative stress and cellular senescence in HK-2 cells.
- BCX promoted nuclear expression of NRF2, preserved mitochondrial function, and reduced mitochondrial damage.
- Silencing NRF2 diminished BCX's protective effects on mitochondria and reversed its anti-oxidative and anti-senescence properties.
Conclusions:
- BCX protects renal cells against oxidative stress-induced senescence by enhancing mitochondrial function through NRF2 nuclear translocation.
- BCX demonstrates potential as a therapeutic strategy for preventing and treating kidney diseases.
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