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. 2025 Apr 24;43(3):23.
doi: 10.1007/s12640-025-00745-3.

The Protective Effect of Annexin A1 on Autophagy Via the CAMK2/BECN1 Signaling Pathway in PC12 Cells Stimulated with H2O2

Shan Hui  1 , Yi Long  2 , Lemei Zhu  3   4 , Junpei Hu  1 , Qing Zheng #  1 , Lihui Liang #  5
Affiliations

The Protective Effect of Annexin A1 on Autophagy Via the CAMK2/BECN1 Signaling Pathway in PC12 Cells Stimulated with H2O2

Shan Hui et al. Neurotox Res. .

Abstract

This study investigates the potential protective role of annexin A1 (ANXA1) in cell models of H2O2-induced Alzheimer's disease. PC12 cells exposed to varying concentrations of H2O2 exhibited a dose-dependent decrease in cell viability. H2O2 exposure led to elevated reactive oxygen species (ROS) levels, reduced superoxide dismutase (SOD) and catalase (CAT) activities, and a decline in ANXA1 protein expression. Under oxidative stress, ANXA1 overexpression increased cell viability, reduced apoptosis rate, enhanced the expression of microtubule-associated protein 3 (LC3) II/I while reducing phosphorylated calcium/calmodulin-dependent protein kinase II (p-CAMK2)/CAMK2 and phosphorylated beclin 1 (p-BECN1)/BECN1. Conversely, ANXA1 knockdown produced contrasting effects. Overexpression of ANXA1, accompanied by administration of KN-93 (a competitive inhibitor of CAMK2), can synergistically diminished p-CAMK2/CAMK2 and p-BECN1/BECN1 levels while significantly increasing LC3 II/I levels, autophagosomes, and autolysosomes. In conclusion, ANXA1 demonstrated a protective role in H2O2-induced oxidative stress damage model in PC12 cells by inhibiting the CAMK2/BECN1 signaling pathway and enhancing autophagy.

Keywords: Alzheimer's disease; Annexin A1; Autophagy; CAMK2/BECN1; Oxidative stress.

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Conflict of interest statement

Declarations. Competing Interests: The authors declare no competing interests.

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