Sevoflurane-induced P300 promotes neuron apoptosis via Sp1/CDK9 pathway
© 2023 John Wiley & Sons Australia, Ltd..
Exposure to sevoflurane leads to serious neurological side effects, including neuronal apoptosis and cognitive impairment. In the mouse model, cyclin dependent kinase 9 (CDK9) was significantly downregulated after exposure to sevoflurane, but the effect of CDK9 on neuronal apoptosis and cognitive impairment after sevoflurane exposure has not been elucidated. Here, we found that the upregulation of P300 by sevoflurane in vitro and in vivo inhibited the expression of CDK9 and induced neuron apoptosis. The effect of sevoflurane on CDK9 expression is based on inhibition of its transcription process. P300 inhibited the binding of Sp1 to DNA by affecting the level of Sp1 acetylation, thereby inhibiting the expression of CDK9, cell-cycle arrest and increasing neuron apoptosis. After the use of P300 inhibitor, the acetylation level of Sp1 decreased, thereby increasing binding in the CDK9 promoter region and exerting anti-apoptosis effects. Mice exposed to sevoflurane using P300 inhibitor also showed decreased levels of apoptosis of cortical cells and a decrease in recent cognitive impairment. In summary, sevoflurane-induced P300 inhibited activity of Sp1 by increasing Sp1 acetylation modification, down-modulates CDK9 expression and promotes the occurrence of neuronal apoptosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:50 |
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| Enthalten in: |
Clinical and experimental pharmacology & physiology - 50(2023), 7 vom: 26. Juli, Seite 541-553 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Xiaoqin [VerfasserIn] |
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| Links: |
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| Themen: |
38LVP0K73A |
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| Anmerkungen: |
Date Completed 05.06.2023 Date Revised 07.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/1440-1681.13771 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354296329 |
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| 520 | |a Exposure to sevoflurane leads to serious neurological side effects, including neuronal apoptosis and cognitive impairment. In the mouse model, cyclin dependent kinase 9 (CDK9) was significantly downregulated after exposure to sevoflurane, but the effect of CDK9 on neuronal apoptosis and cognitive impairment after sevoflurane exposure has not been elucidated. Here, we found that the upregulation of P300 by sevoflurane in vitro and in vivo inhibited the expression of CDK9 and induced neuron apoptosis. The effect of sevoflurane on CDK9 expression is based on inhibition of its transcription process. P300 inhibited the binding of Sp1 to DNA by affecting the level of Sp1 acetylation, thereby inhibiting the expression of CDK9, cell-cycle arrest and increasing neuron apoptosis. After the use of P300 inhibitor, the acetylation level of Sp1 decreased, thereby increasing binding in the CDK9 promoter region and exerting anti-apoptosis effects. Mice exposed to sevoflurane using P300 inhibitor also showed decreased levels of apoptosis of cortical cells and a decrease in recent cognitive impairment. In summary, sevoflurane-induced P300 inhibited activity of Sp1 by increasing Sp1 acetylation modification, down-modulates CDK9 expression and promotes the occurrence of neuronal apoptosis | ||
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