Ac-YVAD-cmk ameliorated sevoflurane-induced cognitive dysfunction and revised mitophagy impairment

Copyright: © 2023 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..

It is common for elderly patients to develop postoperative cognitive dysfunction (POCD), but the pathophysiological mechanisms have not yet been fully explored. NLRP3 inflammasome activation and mitophagy impairment was involved in neurodegenerative disease. This study investigated the interaction of NLRP3 inflammasome and mitophagy in sevoflurane-induced cognitive dysfunction. We found that sevoflurane induced cleaved caspase-1 level, IL-1β and IL-18 maturation, and activated NLRP3 inflammasome in aged mice and the primary hippocampus neuron. The cleaved caspase-1 was demonstrated in microglia of hippocampus. Ac-YVAD-cmk, a selected caspase-1 inhibitor, reduced the expression of cleaved caspase-1, IL-1β, IL-18 and NLRP3 inflammasome activation induced by sevoflurane. Ac-YVAD-cmk ameliorated learning ability impairment in aged mice induced by sevoflurane using Morris water maze. Moreover, Ac-YVAD-cmk reversed the mitophagy flux dysfunction induced by sevoflurane in aged mice by western blotting, immunostaining and mt-Keima reporters. For the first time, we found caspase-1 inhibitor mitigated mitochondria dysfunction and revised mitophagy impairment induced by sevoflurane.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:18

Enthalten in:

PloS one - 18(2023), 1 vom: 01., Seite e0280914

Sprache:

Englisch

Beteiligte Personen:

Zheng, Du [VerfasserIn]
Wang, Hongwei [VerfasserIn]
Zhou, Youfa [VerfasserIn]
Chen, Yeru [VerfasserIn]
Chen, Gang [VerfasserIn]

Links:

Volltext

Themen:

38LVP0K73A
Caspase 1
EC 3.4.22.36
Inflammasomes
Interleukin-18
Journal Article
N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone
NLR Family, Pyrin Domain-Containing 3 Protein
Research Support, Non-U.S. Gov't
Sevoflurane

Anmerkungen:

Date Completed 27.01.2023

Date Revised 17.03.2023

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1371/journal.pone.0280914

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM352069570