[Retracted] Involvement of Mitochondrial Dynamics and Mitophagy in Sevoflurane‐Induced Cell Toxicity

Li, Ming; Guo, Jianqiang; Wang, Hongjie; Li, Yuzhen

doi:10.1155/2021/6685468

Cited by 16 publications

(14 citation statements)

References 89 publications

(111 reference statements)

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“…Even the function of Sev on ferroptosis and mitophagy in cancers has not been reported, although some research demonstrated that Sev induced ferroptosis and mitophagy in other disease models. Exposure of Sev in young age mice was found to trigger mitophagy ( 40 ). Zhao et al.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Zhang

Chen

et al. 2022

Front. Oncol.

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ObjectiveTo clarify the function and mechanisms of sevoflurane (Sev) on ferroptosis in glioma cells.MethodsDifferent concentrations of Sev were used to treat glioma cells U87 and U251. Ferroptosis inducer Erastin was used to incubate glioma cells combined with Sev and ATF4 siRNA transfection treatment. CCK-8 assay and colorimetric assay were performed to analyze cell viability and Fe+ concentration, respectively. The releases of reactive oxygen species (ROS) were determined by flow cytometry analysis. Transcriptional sequencing was used to screen the differential genes affected by Sev in U251 cells. The mRNA and protein expression of ferroptosis-associated genes was detected by qRT-PCR and Western blotting.ResultsSev could suppress cell viability, increase ROS levels and Fe+ concentration, downregulate the protein expression levels of GPX4, and upregulate transferrin, ferritin, and Beclin-1 in a dose-dependent manner in U87 and U251 cells. The expression of ferroptosis and mitophagy-related gene activating transcription factor 4 (ATF4) was identified to be enhanced by Sev analyzed by transcriptional sequencing. ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1), which is involved in ferroptosis, is a downstream gene of ATF4. Inhibition of ATF4 could interrupt the expression of CHAC1 induced by Sev in U87 and U251 cells. Ferroptosis inducer Erastin treatment obviously inhibited the cell viability, elevated the Fe2+ concentration, and promoted ROS generation in U87 and U251 cells. The protein level of ATF4 and CHAC1 was increased in Erastin-treated U87 and U251 cells. Moreover, the interruption of Sev-induced ferroptosis and CHAC1 activating induced by ATF4 suppression could be reversed by Erastin.ConclusionsIn summary, this study suggested that Sev exposure-induced ferroptosis by the ATF4-CHAC1 pathway in glioma cells.

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Section: Discussionmentioning

confidence: 99%

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Zhang

Chen

et al. 2022

Front. Oncol.

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“…Mitochondrial dysfunction has been previously described for sevoflurane in experimental studies [ 14 , 45 , 46 ]. To clarify whether the CMRO 2 decrease by 4% sevoflurane might be related to mitochondrial impairment, we performed FAD imaging to monitor mitochondrial redox state while measuring [K + ] o as a correlate for neuronal activity and [Ca 2+ ] o as the main trigger for intracellular metabolic activation [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane Effects on Neuronal Energy Metabolism Correlate with Activity States While Mitochondrial Function Remains Intact

Maechler

Rösner

Wallach

et al. 2022

IJMS

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During general anesthesia, alterations in neuronal metabolism may induce neurotoxicity and/or neuroprotection depending on the dose and type of the applied anesthetic. In this study, we investigate the effects of clinically relevant concentrations of sevoflurane (2% and 4%, i.e., 1 and 2 MAC) on different activity states in hippocampal slices of young Wistar rats. We combine electrophysiological recordings, partial tissue oxygen (ptiO2) measurements, and flavin adenine dinucleotide (FAD) imaging with computational modeling. Sevoflurane minimally decreased the cerebral metabolic rate of oxygen (CMRO2) while decreasing synaptic transmission in naive slices. During pharmacologically induced gamma oscillations, sevoflurane impaired network activity, thereby decreasing CMRO2. During stimulus-induced neuronal activation, sevoflurane decreased CMRO2 and excitability while basal metabolism remained constant. In this line, stimulus-induced FAD transients decreased without changes in basal mitochondrial redox state. Integration of experimental data and computer modeling revealed no evidence for a direct effect of sevoflurane on key enzymes of the citric acid cycle or oxidative phosphorylation. Clinically relevant concentrations of sevoflurane generated a decent decrease in energy metabolism, which was proportional to the present neuronal activity. Mitochondrial function remained intact under sevoflurane, suggesting a better metabolic profile than isoflurane or propofol.

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“…As one of the important members of the autophagy family, macroautophagy (MA), mitophagy (mA) [47][48][49] and CMA [49][50][51][52], CMA starts with HSC70, and HSC70 targets cargo proteins and then binds to LAMP2A to translocate the proteins into the lysosomal lumen. CMA activity is detectable under basal conditions in most cells, but overactivation occurs during stress, such as nutrient deprivation [53] and lipid overload [54,55].…”

Section: Discussionmentioning

confidence: 99%

Chaperone-mediated autophagy plays an important role in regulating retinal progenitor cell homeostasis

Jin

Chen

et al. 2022

Stem Cell Res Ther

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Purpose To explore the function and regulatory mechanism of IFITM3 in mouse neural retinal progenitor cells (mNRPCs), which was found to be very important not only in the development of the retina in embryos but also in NRPCs after birth. Methods Published single-cell sequencing data were used to analyze IFITM3 expression in mNRPCs. RNA interference was used to knock down the expression of IFITM3. CCK-8 assays were used to analyze cell viability. RNA-seq was used to assess mRNA expression, as confirmed by real-time quantitative PCR, and immunofluorescence assays and western blots were used to validate the levels of relative proteins, and autophagy flux assay. Lysosomal trackers were used to track the organelle changes. Results The results of single-cell sequencing data showed that IFITM3 is highly expressed in the embryo, and after birth, RNA-seq showed high IFITM3 expression in mNRPCs. Proliferation and cell viability were greatly reduced after IFITM3 was knocked down. The cell membrane system and lysosomes were dramatically changed, and lysosomes were activated and evidently agglomerated in RAMP-treated cells. The expression of LAMP1 was significantly increased with lysosome agglomeration after treatment with rapamycin (RAMP). Further detection showed that SQSTM1/P62, HSC70 and LAMP-2A were upregulated, while no significant difference in LC3A/B expression was observed; no autophagic flux was generated. Conclusion IFITM3 regulates mNRPC viability and proliferation mainly through chaperone-mediated autophagy (CMA) but not macroautophagy (MA). IFITM3 plays a significant role in maintaining the homeostasis of progenitor cell self-renewal by sustaining low-level activation of CMA to eliminate deleterious factors in cells.

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[Retracted] Involvement of Mitochondrial Dynamics and Mitophagy in Sevoflurane‐Induced Cell Toxicity

Cited by 16 publications

References 89 publications

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Sevoflurane Effects on Neuronal Energy Metabolism Correlate with Activity States While Mitochondrial Function Remains Intact

Chaperone-mediated autophagy plays an important role in regulating retinal progenitor cell homeostasis

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