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Kidney Week

Abstract: TH-PO082

COPT Nanoparticles Ameliorate the AKI-to-CKD Transition via Inducing BNIP3-Mediated Mitophagy

Session Information

  • AKI: Mechanisms - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Huang, Yinghui, Army Medical University, Chongqing, Chongqing, China
  • Zhao, Jinghong, Army Medical University, Chongqing, Chongqing, China

Group or Team Name

  • Dept of Nephrology, Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University.
Background

Accumulating evidence highlights mitochondrial dysfunction as a crucial factor in the pathogenesis of acute kidney injury (AKI), thus novel therapeutic strategies maintaining mitochondrial homeostasis are highly anticipated. Recent studies have shown that cobaltosic oxide has peroxidase-like catalytic activities, although its role and mechanism remain elusive in AKI.

Methods

Cobaltosic oxide-polyethylene glycol-triphenylphosphine (COPT) nanoparticles were synthesized by conjugating cobaltosic oxide with polyethylene glycol and triphenylphosphine. Its theranostic effect was evaluated by using AKI mice, zebrafishes and cells.

Results

COPT preferentially accumulated in the renal proximal tubule cells, and significantly alleviated ischemic AKI in mouse and zebrafish models. COPT also inhibited the transition from AKI to chronic kidney disease (CKD), with few side effects. Further, COPT localized in the mitochondria, and ameliorated hypoxia-reoxygenation (HR)-mediated mitochondrial damage through enhancing mitophagy. Mechanistically, COPT dose-dependently induced the expression of Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3), while knockdown of BNIP3 attenuated COPT-induced mitophagic flux and mitochondrial protection.

Conclusion

COPT nanoparticles ameliorate AKI and its progression to CKD through inducing BNIP3-mediated mitophagy, indicating that COPT may serve as a promising mitochondria-targeting therapeutic agent against AKI.