Integrated insight into the molecular mechanisms of selenium-modulated, MPP+-induced cytotoxicity in a Parkinson’s disease model

ElsevierVolume 79, September 2023, 127208Journal of Trace Elements in Medicine and BiologyAuthor links open overlay panel, , , , , , , , , AbstractObjective

Parkinson’s disease (PD) is a neurodegenerative disease that is associated with oxidative stress. Due to the anti-inflammatory and antioxidant functions of Selenium (Se), this molecule may have neuroprotective functions in PD; however, the involvement of Se in such a protective function is unclear.

Methods

1-methyl-4-phenylpyridinium (MPP+), which inhibits mitochondrial respiration, is generally used to produce a reliable cellular model of PD. In this study, a MPP+-induced PD model was used to test if Se could modulate cytotoxicity, and we further capture gene expression profiles following PC12 cell treatment with MPP+ with or without Se by genome wide high-throughput sequencing.

Results

We identified 351 differentially expressed genes (DEGs) and 14 differentially expressed long non-coding RNAs (DELs) in MPP+-treated cells when compared to controls. We further document 244 DEGs and 27 DELs in cells treated with MPP+ and Se vs. cells treated with MPP+ only. Functional annotation analysis of DEGs and DELs revealed that these groups were enriched in genes that respond to reactive oxygen species (ROS), metabolic processes, and mitochondrial control of apoptosis. Thioredoxin reductase 1 (Txnrd1) was also identified as a biomarker of Se treatment.

Conclusions

Our data suggests that the DEGs Txnrd1, Siglec1 and Klf2, and the DEL AABR07044454.1 which we hypothesize to function in cis on the target gene Cdkn1a, may modulate the underlying neurodegenerative process, and act a protective function in the PC12 cell PD model. This study further systematically demonstrated that mRNAs and lncRNAs induced by Se are involved in neuroprotection in PD, and provides novel insight into how Se modulates cytotoxicity in the MPP+-induced PD model.

AbbreviationsGPx

glutathione peroxidase

Sephs2

selenophosphate synthetase 2

Txnrd1

thioredoxin reductase 1

Txnrd 2

thioredoxin reductase 2

Txnrd 3

thioredoxin reductase 3

MPP+

1-methyl-4-phenylpyridinium

DEG

differential expression of gene

DEL

differential expression of lncRNA

CCK-8

cell counting kit-8 assay

ROS

reactive oxygen species

Klf2

krueppel-like factor 2

Cdkn1a

Cyclin-dependent kinase inhibitor 1

KEGG

Kyoto Encyclopedia of Genes and Genomes

Keywords

Parkinson’s disease

Selenium

RNA-seq

MRNA

LncRNA

© 2023 The Authors. Published by Elsevier GmbH.

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