L1 modulates protein kinase D1 (PKD1) phosphorylation 
during H2O2-induced cell senescence

Xia Mi; Yu Peng; Heng Wu; Shuangxi Chen; Weijiang Zhao

doi:10.5114/fn.2025.155146

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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abstract:

Original paper

L1 modulates protein kinase D1 (PKD1) phosphorylation during H2O2-induced cell senescence

Xia Mi

^{1, 2, 3}

,

Yu Peng

^{1, 2}

,

Heng Wu

^{1, 2}

,

Shuangxi Chen

^{1, 2}

,

Weijiang Zhao

⁴

The First Affiliated Hospital, Department of Neurology, Multi-Omics Research Center for Brain Disorders, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Clinical Research Center for Immune-Related Encephalopathy in Hunan Province, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Department of Neonatology, Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410000, Hunan, PR China
Department of Cell Biology, Wuxi School of Medicine, Jiangnan University, 1800 Lihu Dadao, Binhu District, Wuxi, Jiangsu, 214122, PR China

Folia Neuropathol 2025; 63 (4)

DOI: https://doi.org/10.5114/fn.2025.155146

Online publish date: 2025/10/13

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Age-dependent oxidative stress is considered to be involved in degenerative processes in age-related neurodegenerative disorders. The L1 cell adhesion molecule (L1CAM or L1) plays an essential role in the regeneration process following neural lesions in the adult nervous system. Protein kinase D1 (PKD1) is increasingly implicated in neuroprotection. Hence, the present study aimed to investigate the possible functional association between L1 and phosphorylated PKD1 (pPKD1) in oxidative stress-induced senescence. The study revealed that recombinant L1 (rL1) upregulated PKD1 phosphorylation, the pErk1/2 level and the Bcl2/Bax ratio in SK-N-SH cells in a concentration-dependent manner, with a peak level observed at 5 nM. L1 also increased the pPKD1 level in human pluripotent stem cells. In the 20 µM H2O2-induced senescence SK-N-SH cell model, L1 also increased the pPKD1 level and decreased the number of SA-b-gal-positive cells. On the whole, the results of the present study suggest that L1 is capable of modulating PKD1 phosphorylation to inhibit oxidative stress-induced senescence.

keywords:

L1 modulates protein kinase D1 (PKD1) phosphorylation during H2O2-induced cell senescence

Xia Mi 1, 2, 3 , Yu Peng 1, 2 , Heng Wu 1, 2 , Shuangxi Chen 1, 2 , Weijiang Zhao 4

L1 cell adhesion molecule, PKD1 phosphorylation, senescence

Xia Mi

^{1, 2, 3}

,

Yu Peng

^{1, 2}

,

Heng Wu

^{1, 2}

,

Shuangxi Chen

^{1, 2}

,

Weijiang Zhao

⁴