TSPO Ligands Protect against Neuronal Damage Mediated by LPS-Induced BV-2 Microglia Activation

Ma, Baoyu; Liu, Yongxin; Zhang, Xiao; Zhang, Rui; Zhang, Zhenjiang; Zhang, Zhihao; Liu, Jie; Juan, Zhaodong; Sun, Xiaotong; Sun, Lina; Huang, Jingyao

doi:10.1155/2022/5896699

Cited by 7 publications

(6 citation statements)

References 40 publications

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“…This facilitating effect of TSPO in increasing the inflammatory response that we demonstrated is corroborated in vivo by the presence of a decrease in the ability of LPS to induce inflammation in animals previously treated with a TSPO antagonist. , Microglia also shows an ameliorating effect of pharmacological TSPO inhibition upon LPS exposure . Such a protective effect of TSPO inhibition has also been hypothesized in various other pathologies (multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease ,, ) and could therefore indicate a pro-inflammatory function of the TSPO.…”

Section: Discussionsupporting

confidence: 80%

“…5,6 Microglia also shows an ameliorating effect of pharmacological TSPO inhibition upon LPS exposure. 54 Such a protective effect of TSPO inhibition has also been hypothesized in various other pathologies (multiple sclerosis, Alzheimer's disease, and Parkinson's disease 7,8,55 ) and could therefore indicate a pro-inflammatory function of the TSPO.…”

Section: Discussionmentioning

confidence: 90%

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18 kDa Translocator Protein TSPO Is a Mediator of Astrocyte Reactivity

et al. 2023

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An increase in astrocyte reactivity has been described in Alzheimer’s disease and seems to be related to the presence of a pro-inflammatory environment. Reactive astrocytes show an increase in the density of the 18 kDa translocator protein (TSPO), but TSPO involvement in astrocyte functions remains poorly understood. The goal of this study was to better characterize the mechanisms leading to the increase in TSPO under inflammatory conditions and the associated consequences. For this purpose, the C6 astrocytic cell line was used in the presence of lipopolysaccharide (LPS) or TSPO overexpression mediated by the transfection of a plasmid encoding TSPO. The results show that nonlethal doses of LPS induced TSPO expression at mRNA and protein levels through a STAT3-dependent mechanism and increased the number of mitochondria per cell. LPS stimulated reactive oxygen species (ROS) production and decreased glucose consumption (quantified by the [18F]FDG uptake), and these effects were diminished by FEPPA, a TSPO antagonist. The transfection-mediated overexpression of TSPO induced ROS production, and this effect was blocked by FEPPA. In addition, a synergistic effect of overexpression of TSPO and LPS on ROS production was observed. These data show that the increase of TSPO in astrocytic cells is involved in the regulation of glucose metabolism and in the pro-inflammatory response. These data suggest that the overexpression of TSPO by astrocytes in Alzheimer’s disease would have rather deleterious effects by promoting the pro-inflammatory response.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 90%

18 kDa Translocator Protein TSPO Is a Mediator of Astrocyte Reactivity

et al. 2023

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“…Western blot analysis was performed as described previously with minor modifications [ 26 ]. The cells were lysed with RIPA lysis buffer (#P0013B, Beyotime Biotechnology, Shanghai, China) containing 1% protease and phospholipase inhibitor on ice for 30 min and centrifuged at 12,000 rpm in a cold centrifuge at 4° C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effects of Salvianolic Acid B on Angiotensin II–Induced Atrial Fibrosis by Regulating Atrium Metabolism via Targeting AMPK/FoxO1/miR-148a-3p Axis

Liu

Sun

et al. 2022

J. of Cardiovasc. Trans. Res.

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The present study highlights the effects of salvianolic acid B (Sal B) on angiotensin II (Ang II)–activated atrial fibroblasts as well as the associated potential mechanism from the metabonomics perspective. Metabolic profile analysis performed an optimal separation of the Ang II and control group, indicating a recovery impact of Sal B on Ang II–activated fibroblasts (FBs). We found that metabolite levels in the Ang II + Sal B group were reversed to normal. Moreover, 23 significant metabolites were identified. Metabolic network analysis indicated that these metabolites participated in purine metabolism and FoxO signaling pathway. We found that Sal B activated AMP-activated protein kinase (AMPK) phosphorylation, which further promoted FoxO1 activation and increased miR-148a-3p level. We further verified that Sal B modulate the abnormal AMP, phosphocreatine, glutathione (GSH), and reactive oxygen species (ROS) production in Ang II–stimulated FBs. Collectively, Sal B can protect the Ang II–activated FBs from fibrosis and oxidative stress via AMPK/FoxO1/miRNA-148a-3p axis. Graphical abstract

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“…After exposure to air, the specimens were observed under transmission electron microscopy (EM UC7; Leica Microsystems GmbH) to analyze the morphology of the nuclear membranes and mitochondria. The specific method was consistent with that used by Ma et al (17).…”

Section: Determination Of H 2 O 2 Concentration Needed To Induce Os K...mentioning

confidence: 59%

Protective effect of L‑carnitine against oxidative stress injury in human ovarian granulosa cells

et al. 2023

Exp Ther Med

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Granulosa cells (GCs) are important for supporting and nourishing oocytes during follicular development and maturation. Oxidative stress (OS) injury of GCs can lead to decreased responsiveness of follicles to follicular stimulating hormone (FSH), which will accelerate ovarian senescence and adversely affect oocyte and embryo quality. Since L-carnitine has been previously reported to exert strong antioxidant activity, the present study aimed to explore the possible effects of L-carnitine on OS injury and FSH receptor (FSHR) expression in ovarian GCs, results of which may be of significance for GCs protection. In the present study, OS was induced in vitro in KGN cells by treatment with H 2 O 2 . KGN cells were cultured and divided into the following four groups: Blank, OS, and 40 and 80 µmol/l L-carnitine pre-treatment groups. In the OS group, cells showed nuclear pyknosis, mitochondria swelled irregularly whilst featuring fractured cristae. In addition, cell viability, ROS levels, superoxide dismutase levels, glutathione levels, malondialdehyde levels, the mitochondrial membrane potential and FSHR expression, as determined by Cell Counting Kit-8 (CCK-8), 2,7-dichloro-dihydrofluorescein diacetate, spectrophotometry, ELISA, spectrophotometry, JC-1 and western blot analyses, respectively, were all significantly different in the OS group compared with those in the control group. However, malonaldehyde levels, reactive oxygen species levels and the apoptosis rate according to flow cytometry were all significantly increased compared with those in the control. Compared with those in the OS group, the morphology of cells and mitochondria in the L-carnitine pre-treatment groups were improved, whilst cell viability and the expression of FSHR were significantly increased but oxidative stress injury was decreased. The present results suggest that L-carnitine can protect the cells from OS damage induced by H 2 O 2 , enhance antioxidant activity whilst suppressing the apoptosis of GCs, in addition to preserving FSHR expression in GCs under OS. Therefore, the present study revealed that the introduction of L-carnitine in clinical medicine or dietary supplement may protect GCs, improve follicular quality and female reproductive function.

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TSPO Ligands Protect against Neuronal Damage Mediated by LPS-Induced BV-2 Microglia Activation

Cited by 7 publications

References 40 publications

18 kDa Translocator Protein TSPO Is a Mediator of Astrocyte Reactivity

18 kDa Translocator Protein TSPO Is a Mediator of Astrocyte Reactivity

Therapeutic Effects of Salvianolic Acid B on Angiotensin II–Induced Atrial Fibrosis by Regulating Atrium Metabolism via Targeting AMPK/FoxO1/miR-148a-3p Axis

Protective effect of L‑carnitine against oxidative stress injury in human ovarian granulosa cells

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