Enhanced oxidative phosphorylation, re-organized intracellular signaling, and epigenetic de-silencing as revealed by oligodendrocyte translatome analysis after contusive spinal cord injury
© 2023. The Author(s)..
Reducing the loss of oligodendrocytes (OLs) is a major goal for neuroprotection after spinal cord injury (SCI). Therefore, the OL translatome was determined in Ribotag:Plp1-CreERT2 mice at 2, 10, and 42 days after moderate contusive T9 SCI. At 2 and 42 days, mitochondrial respiration- or actin cytoskeleton/cell junction/cell adhesion mRNAs were upregulated or downregulated, respectively. The latter effect suggests myelin sheath loss/morphological simplification which is consistent with downregulation of cholesterol biosynthesis transcripts on days 10 and 42. Various regulators of pro-survival-, cell death-, and/or oxidative stress response pathways showed peak expression acutely, on day 2. Many acutely upregulated OL genes are part of the repressive SUZ12/PRC2 operon suggesting that epigenetic de-silencing contributes to SCI effects on OL gene expression. Acute OL upregulation of the iron oxidoreductase Steap3 was confirmed at the protein level and replicated in cultured OLs treated with the mitochondrial uncoupler FCCP. Hence, STEAP3 upregulation may mark mitochondrial dysfunction. Taken together, in SCI-challenged OLs, acute and subchronic enhancement of mitochondrial respiration may be driven by axonal loss and subsequent myelin sheath degeneration. Acutely, the OL switch to oxidative phosphorylation may lead to oxidative stress that is further amplified by upregulation of such enzymes as STEAP3.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Scientific reports - 13(2023), 1 vom: 01. Dez., Seite 21254 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Forston, Michael D [VerfasserIn] |
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Date Completed 04.12.2023 Date Revised 21.12.2023 published: Electronic UpdateOf: Res Sq. 2023 Jul 28;:. - PMID 37546871 Citation Status MEDLINE |
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| doi: |
10.1038/s41598-023-48425-6 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365317918 |
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| 100 | 1 | |a Forston, Michael D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Enhanced oxidative phosphorylation, re-organized intracellular signaling, and epigenetic de-silencing as revealed by oligodendrocyte translatome analysis after contusive spinal cord injury |
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| 500 | |a Date Revised 21.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateOf: Res Sq. 2023 Jul 28;:. - PMID 37546871 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Reducing the loss of oligodendrocytes (OLs) is a major goal for neuroprotection after spinal cord injury (SCI). Therefore, the OL translatome was determined in Ribotag:Plp1-CreERT2 mice at 2, 10, and 42 days after moderate contusive T9 SCI. At 2 and 42 days, mitochondrial respiration- or actin cytoskeleton/cell junction/cell adhesion mRNAs were upregulated or downregulated, respectively. The latter effect suggests myelin sheath loss/morphological simplification which is consistent with downregulation of cholesterol biosynthesis transcripts on days 10 and 42. Various regulators of pro-survival-, cell death-, and/or oxidative stress response pathways showed peak expression acutely, on day 2. Many acutely upregulated OL genes are part of the repressive SUZ12/PRC2 operon suggesting that epigenetic de-silencing contributes to SCI effects on OL gene expression. Acute OL upregulation of the iron oxidoreductase Steap3 was confirmed at the protein level and replicated in cultured OLs treated with the mitochondrial uncoupler FCCP. Hence, STEAP3 upregulation may mark mitochondrial dysfunction. Taken together, in SCI-challenged OLs, acute and subchronic enhancement of mitochondrial respiration may be driven by axonal loss and subsequent myelin sheath degeneration. Acutely, the OL switch to oxidative phosphorylation may lead to oxidative stress that is further amplified by upregulation of such enzymes as STEAP3 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Wei, George Z |e verfasserin |4 aut | |
| 700 | 1 | |a Chariker, Julia H |e verfasserin |4 aut | |
| 700 | 1 | |a Stephenson, Tyler |e verfasserin |4 aut | |
| 700 | 1 | |a Andres, Kariena |e verfasserin |4 aut | |
| 700 | 1 | |a Glover, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Rouchka, Eric C |e verfasserin |4 aut | |
| 700 | 1 | |a Whittemore, Scott R |e verfasserin |4 aut | |
| 700 | 1 | |a Hetman, Michal |e verfasserin |4 aut | |
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