Potential involvement of the 18 kDa translocator protein and reactive oxygen species in apoptosis of THP-1 macrophages induced by sonodynamic therapy

Sun, Xin; Guo, Shuyuan; Wang, Wei; Cao, Zhengyu; Dan, Juhua; Cheng, Jiali; Cao, Wei; Tian, Fang; Cao, Wenwu; Tian, Ye

doi:10.1371/journal.pone.0196541

Cited by 14 publications

(8 citation statements)

References 29 publications

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“…Taking into account that TSPO is also involved in alterations of cytosolic cholesterol levels, there is also a possibility for its involvement in modulation of α-Syn aggregation rates. Connection has also been established between TSPO binding capacity and ROS levels, which are as mentioned earlier one of the reasons for PD development [89,90]. In accordance with these findings, Gatliff et al reported that SH-SY5H cells exhibited enhanced ROS production after TSPO overexpression establishing connection between TSPO, VDAC, and Ca 2+ homeostasis [91].…”

Section: α-Synuclein Lipid Homeostasis and Tsposupporting

confidence: 64%

Alpha-Synuclein Aggregation, Cholesterol Transport, and the 18-kDa Translocator Protein

Dimitrova-Shumkovska¹,

Krstanoski²

2020

Synucleins - Biochemistry and Role in Diseases

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The molecular responses to counteract diseases, including insulting conditions such as injury and pathogen infection, involve coordinated modulation of gene expression programs. The association of alpha synuclein (α-Syn) with several progressive disorders has focused the research on its induced conformational behavior as critical for uncovering the "secrets" for progression of α-synucleinopathies. Cholesterol is one of the lipid components crucial for regular proliferation of the nervous tissue. Its interaction with α-Syn may offer other insights to α-Syn normal expression. Discovering that the molecular regulatory mechanisms responsible for prevention of α-Syn aggregation may be manifested through microRNA (miRNA) regulated gene expression is also crucial for widening the perception of neuropathology. The 18-kDa translocator protein (TSPO) localized on the outer mitochondrial membrane is able to regulate various cellular and tissue functions, with key role as cholesterol transporter for neurosteroid synthesis. TSPO up-regulation, has been connected to several diseases, including cancer, neuronal damage, and inflammation. Connection may also be established between TSPO expression and fatty acid oxidation, thus unveiling new possibilities in the research of α-Syn overexpression. However, expression of TSPO in the neuroinflammatory environment is probably the best starting point for targeting TSPO as a suitable therapeutic target.

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Section: α-Synuclein Lipid Homeostasis and Tsposupporting

confidence: 64%

Alpha-Synuclein Aggregation, Cholesterol Transport, and the 18-kDa Translocator Protein

Dimitrova-Shumkovska¹,

Krstanoski²

2020

Synucleins - Biochemistry and Role in Diseases

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“…Other cell types should be chosen for the study but we elected to use it since THP-1 macrophages were used by some researchers. 34,35 We also need further studies in human blood-derived macrophages and mouse models to confirm our conclusion.…”

Section: F I G U R Ementioning

confidence: 78%

Exosomal miR‐103‐3p from LPS‐activated THP‐1 macrophage contributes to the activation of hepatic stellate cells

Chen

Yao

et al. 2020

The FASEB Journal

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Hepatic fibrosis occurs during chronic hepatic injury and is involved in hepatic stellate cells (HSCs) activated by several types of immune cells. Among the immune cells, hepatic macrophages and their crosstalk with HSCs play a vital role in all stages of hepatic fibrosis. Exosomes, which are 30‐150 nm lipid bilayer vehicles, can transfer specific lipid, nucleic acids, proteins, and other bioactive molecules. Exosomes can act as good communication between macrophages and HSCs. Herein, we investigated the role of exosomes between THP‐1 macrophage and HSCs in the progression of liver fibrosis. Exosomes originating from lipopolysaccharide (LPS)‐treated THP‐1 macrophages promoted HSCs proliferation and induced the increased expression of fibrotic genes. LPS could alter the miRNA profile in exosomes secreted from THP‐1 macrophages. The changed miR‐103‐3p in exosomes could promote HSCs proliferation and activation by targeting Krüppel‐like factor 4 (KLF4) and it plays important roles in the crosstalk between THP‐1 macrophages and HSCs during the progression of liver fibrosis. Moreover, miR‐103‐3p in serum exosomes from liver fibrosis patients could be a biomarker for liver fibrosis. Therefore, exosomes may have important roles in the crosstalk between macrophage and HSCs in the progression of chronic liver diseases.

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“…Herein, another pro-inflammatory signaling parameter explored was the level of the reactive oxygen species. The treatment with PK-11195 has been reported to decrease ROS production in human macrophages [73] and in murine microglia [48]; herein, TSPO ligands were able to modulate the production of ROS in human microglia too. Although the mechanism of TSPO regulation of ROS production is still under debate, the obtained results supports that this ability is not related to steroidogenesis stimulation.…”

Section: Discussionmentioning

confidence: 93%

Microglial Pro-Inflammatory and Anti-Inflammatory Phenotypes Are Modulated by Translocator Protein Activation

Pozzo

Tremolanti

Costa

et al. 2019

IJMS

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A key role of the mitochondrial Translocator Protein 18 KDa (TSPO) in neuroinflammation has been recently proposed. However, little is known about TSPO-activated pathways underlying the modulation of reactive microglia. In the present work, the TSPO activation was explored in an in vitro human primary microglia model (immortalized C20 cells) under inflammatory stimulus. Two different approaches were used with the aim to (i) pharmacologically amplify or (ii) silence, by the lentiviral short hairpin RNA, the TSPO physiological function. In the TSPO pharmacological stimulation model, the synthetic steroidogenic selective ligand XBD-173 attenuated the activation of microglia. Indeed, it reduces and increases the release of pro-inflammatory and anti-inflammatory cytokines, respectively. Such ligand-induced effects were abolished when C20 cells were treated with the steroidogenesis inhibitor aminoglutethimide. This suggests a role for neurosteroids in modulating the interleukin production. The highly steroidogenic ligand XBD-173 attenuated the neuroinflammatory response more effectively than the poorly steroidogenic ones, which suggests that the observed modulation on the cytokine release may be influenced by the levels of produced neurosteroids. In the TSPO silencing model, the reduction of TSPO caused a more inflamed phenotype with respect to scrambled cells. Similarly, during the inflammatory response, the TSPO silencing increased and reduced the release of pro-inflammatory and anti-inflammatory cytokines, respectively. In conclusion, the obtained results are in favor of a homeostatic role for TSPO in the context of dynamic balance between anti-inflammatory and pro-inflammatory mediators in the human microglia-mediated inflammatory response. Interestingly, our preliminary results propose that the TSPO expression could be stimulated by NF-κB during activation of the inflammatory response.

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Potential involvement of the 18 kDa translocator protein and reactive oxygen species in apoptosis of THP-1 macrophages induced by sonodynamic therapy

Cited by 14 publications

References 29 publications

Alpha-Synuclein Aggregation, Cholesterol Transport, and the 18-kDa Translocator Protein

Alpha-Synuclein Aggregation, Cholesterol Transport, and the 18-kDa Translocator Protein

Exosomal miR‐103‐3p from LPS‐activated THP‐1 macrophage contributes to the activation of hepatic stellate cells

Microglial Pro-Inflammatory and Anti-Inflammatory Phenotypes Are Modulated by Translocator Protein Activation

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