Autophagy activation attenuates the neurotoxicity of local anesthetics by decreasing caspase-3 activity in rats

Xue, Xing; Lv, Ying; Leng, Yufang; Zhang, Yan

doi:10.1016/j.bjane.2020.11.001

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…Studies have con rmed that autophagy has a negative feedback regulation effect on mTOR [16][17]. Caspase-3, which exists in the cytoplasm in the form of zymogen, is activated to generate the active fragment cleaved caspase-3 and the cleavage of PARP1 is regarded as one of the signs of cell apoptosis [18]. LC3 is a substrate that initiates autophagy and forms autophagosomes.…”

Section: Discussionmentioning

confidence: 99%

Effect of Oxidative Stress-Induced Autophagy on Proliferation and Apoptosis of hMSCs

Liu

Zheng

et al. 2022

Preprint

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Background:Objective:To observe the effect of H2O2 induced oxidative stress on autophagy and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs).Method: The hBMSCs were separated and cultured by density gradient centrifugation combined with adherence method. They were divided into blank group (with medium only), 3-MA (autophagy inhibitor) pretreatment group (with 2 ml of 5 mM 3-MA medium), H2O2 Intervention group (add 2ml medium containing 0.05mM H2O2), H2O2+3-MA treatment group (add 2ml medium containing 5mM 3-MA, then add 2ml medium containing 0.05mM H2O2). DCFH-DA staining was used to detect cellular reactive oxygen species (ROS) levels,and CCK-8 analysis was used to detect the effects of different concentrations (0,50,100,200,400μmol/L) of H2O2 on the proliferation of hBMSCs; Monodansylcadaverine(MDC) Fluorescent amine probe staining, Lysosome Red Fluorescent Probe (Lyso-Tracker Red) staining to observe the level of autophagy; Immunofluorescence staining to detect the expression of LC3A/B; Flow cytometry (Annexin V/PI) to detect cell apoptosis Circumstances; Protein chip detection of autophagy-related proteins; Western blot detection of Beclin1, mTOR, p-mTOR, LC3A/B, and Cleaved caspase-3 protein expression.Result: After treating hBMSCs with different concentrations of H2O2 (0,50,100,200,400μmol) for 24h ,48h, and 72h, with the increase of H2O2 concentration, the cell proliferation ability decreased; while with the extension of time, the cell proliferation ability increased not significantly; 50μmol cell proliferation ability is the strongest. Compared with the blank group and 3-MA group, the H2O2 intervention group increased the level of intracellular ROS, increased autophagosomes, and significantly decreased the apoptosis rate; up-regulated Beclin1, mTOR, LC3A/B and Cleaved caspase-3 protein expression, and down-regulated p-mTOR Protein expression level. Compared with the autophagy inhibitor 3-MA group, the H2O2+3-MA group increased the level of intracellular ROS, increased autophagosomes, and did not significantly increase the apoptosis rate; up-regulated the protein expression of Beclin1, mTOR, LC3A/B and Cleaved caspase-3 Down-regulate the expression of p-mTOR protein.Conclusion: H2O2 can induce hMSCs to produce oxidative stress response. Under oxidative stress conditions, hMSCs can promote protective autophagy and reduce cell apoptosis or the level of apoptosis caused by excessive autophagy.

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Section: Discussionmentioning

confidence: 99%

Effect of Oxidative Stress-Induced Autophagy on Proliferation and Apoptosis of hMSCs

Liu

Zheng

et al. 2022

Preprint

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“…Moreover, autophagy plays a role in clearing abnormal TDP-43 ( Huang, Yan & Zhang, 2020 ; Kumar et al, 2021 ), and overexpression of TDP-43 in self-defense under pathological conditions can activate autophagy ( Wang et al 2015a ; Wang et al 2015b ). Moreover, Caspase-3, the end product of apoptosis, is closely related to autophagy ( Gu et al, 2021 ; Xue et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of icaritin on autophagy-related protein expression in TDP-43-transfected SH-SY5Y cells

Zhou

Huang

et al. 2022

PeerJ

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Objective To study the protective effect and mechanism of icaritin (ICT) in a SH-SY5Y cells with virus-loaded TAR DNA-binding domain protein 43(TDP-43) by examining the effect of ICT on the expression of autophagy-related proteins in TDP-43-infected SH-SY5Y cells. Methods A TDP-43-induced neuronal cell injury model was established by transfecting well-growing SH-SY5Y cells with virus loaded with the TDP-43 gene. The changes in cell viability were detected by the CCK-8 method. After successful transfection, the establishment of the model was verified by real-time quantitative PCR (qPCR) and Western blot methods. After the cells were subjected to drug intervention with ICT, the changes in the expression levels of TDP-43, cleaved Caspase-3, LC3 II/I, Beclin-1 and p62 were detected by Western blotting. Results After ICT intervention, it was found that compared with that of the TDP-43 group, the cell viability of the TDP-43+ICT group increased, the expression level of TDP-43 decreased, and the expression levels of the apoptotic protein cleaved Caspase-3, autophagy protein Beclin-1, and LC3-II/I decreased, while the expression level of the autophagy protein p62 increased. Conclusion ICT has a protective effect on the SH-SY5Y cell injury model transfected with TDP-43. This protective effect may be related to reducing the protein expression of TDP-43 and inhibiting autophagy.

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Anesthesia and dementia: An up-to-date review of the existing literature

Tsolaki

Sia

Giannouli

2022

Applied Neuropsychology: Adult

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Autophagy activation attenuates the neurotoxicity of local anesthetics by decreasing caspase-3 activity in rats

Cited by 3 publications

References 28 publications

Effect of Oxidative Stress-Induced Autophagy on Proliferation and Apoptosis of hMSCs

Effect of Oxidative Stress-Induced Autophagy on Proliferation and Apoptosis of hMSCs

Effect of icaritin on autophagy-related protein expression in TDP-43-transfected SH-SY5Y cells

Anesthesia and dementia: An up-to-date review of the existing literature

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