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Investigation of the Hydrogen Sulfide Signaling Pathway in Schwann Cells during Peripheral Nerve Degeneration: Multi-Omics Approaches

Title
Investigation of the Hydrogen Sulfide Signaling Pathway in Schwann Cells during Peripheral Nerve Degeneration: Multi-Omics Approaches
Author(s)
Chun, Yoo LimEom, Won-JoonLee, Jun HyungNguyen, Thy Ngoc ChauPark, Ki-HoonChung,Hyung-JooSeo, HanHuh, YoungbuhmKim, Sang HoonYeo, Seung GeunPark, WonseokBang, GeulKim, Jin YoungKim, Min-SikJeong, Na YoungJung, Junyang
Issued Date
2022-08
Citation
Antioxidants, v.11, no.8
Type
Article
Author Keywords
hydrogen sulfidemulti-omicsN-ethylmaleimide (NEM)oxidative stressperipheral nerve degenerationSchwann cells
Keywords
H2SNF-KAPPA-BOXIDATIVE STRESSPHOSPHORYLATIONPROGRESSIONACTIVATIONRELEASEGAMMAMICE
ISSN
2076-3921
Abstract
N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H2S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an alpha,beta-unsaturated carboxyl compound, on H2S signaling in in vitro- and ex vivo-dedifferentiated Schwann cells using global proteomics (LC-MS) and transcriptomics (whole-genome and small RNA-sequencing (RNA-seq)) methods. The multi-omics analyses identified several genes and proteins related to oxidative stress, such as Sod1, Gnao1, Stx4, Hmox2, Srxn1, and Edn1. The responses to oxidative stress were transcriptionally regulated by several transcription factors, such as Atf3, Fos, Rela, and Smad2. In a functional enrichment analysis, cell cycle, oxidative stress, and lipid/cholesterol metabolism were enriched, implicating H2S signaling in Schwann cell dedifferentiation, proliferation, and myelination. NEM-induced changes in the H2S signaling pathway affect oxidative stress, lipid metabolism, and the cell cycle in Schwann cells. Therefore, regulation of the H2S signaling pathway by NEM during PND could prevent Schwann cell demyelination, dedifferentiation, and proliferation.
URI
http://hdl.handle.net/20.500.11750/16915
DOI
10.3390/antiox11081606
Publisher
MDPI AG
Related Researcher
  • 김민식 Kim, Min-Sik
  • Research Interests Mass Spectrometry; Proteomics; Cancer Proteogenomics; Biomarker Discovery; Integrative Multi-Omics; LC-MS
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Department of New Biology Laboratory for QBIO and Precision Medicine 1. Journal Articles

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