Programmed cell death 4 blocks autophagy and promotes dopaminergic neuronal injury in Parkinson's disease

Cao,Guiling; Kang,Tao; Li,Nini; Li,Peng

doi:10.3892/etm.2024.12423

Programmed cell death 4 blocks autophagy and promotes dopaminergic neuronal injury in Parkinson's disease

Authors:
- Guiling Cao
- Tao Kang
- Nini Li
- Peng Li
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Affiliations: Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: February 12, 2024 https://doi.org/10.3892/etm.2024.12423
Article Number: 135
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dysregulation of autophagy has previously been associated with the formation of toxic proteins, such as α‑synuclein, in patients with Parkinson's disease (PD). In addition, it has been indicated that programmed cell death 4 (PDCD4) can inhibit autophagy in certain conditions, such as diabetic nephropathy, atherosclerosis and cardiac hypertrophy. Therefore, the hypothesis that PDCD4 can promote dopaminergic neuron damage through autophagy was proposed. To explore this hypothesis, the present study treated human neuroblastoma SK‑N‑SH cells with 1‑methyl‑4‑phenylpyridinium (MPP⁺) to establish an in vitro model of PD. The potential effects of PDCD4 knockdown on lactate dehydrogenase (LDH) release, cell apoptosis, inflammatory response, oxidative stress and autophagy were then evaluated in this model of PD using an LDH assay kit, flow cytometry, western blotting, ELISA and immunofluorescence. The autophagy inhibitor 3‑methyladenine (3‑MA) was also applied to treat these cells, and its effects on these aforementioned parameters following PDCD4 knockdown were assessed. MPP⁺ was shown to increase the expression levels of PDCD4 in SK‑N‑SH cells. PDCD4 knockdown was revealed to suppress LDH release, cell apoptosis, secretion of inflammatory factors and oxidative stress. In addition, PDCD4 knockdown was demonstrated to enhance autophagy in cells treated with MPP⁺. By contrast, 3‑MA treatment reversed the aforementioned effects of PDCD4 knockdown on cells, suggesting autophagy to be among the processes regulated by PDCD4 in SK‑N‑SH cells. The results of the present study suggested the existence of regulatory effects mediated by PDCD4 on autophagy in MPP⁺‑induced SK‑N‑SH cells, offering potential future targets for PD therapy.

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