Bader, Stefanie and Wolf, Luisa and Milenkovic, Vladimir M. and Gruber, Michael and Nothdurfter, Caroline and Rupprecht, Rainer and Wetzel, Christian H. (2019) Differential effects of TSPO ligands on mitochondrial function in mouse microglia cells. PSYCHONEUROENDOCRINOLOGY, 106. pp. 65-76. ISSN 0306-4530,
Full text not available from this repository. (Request a copy)Abstract
The translocator protein 18 kDa (TSPO), initially characterized as peripheral benzodiazepine receptor, is a conserved outer mitochondrial membrane protein, implicated in cholesterol transport thereby affecting steroid hormone biosynthesis, as well as in general mitochondrial function related to bioenergetics, oxidative stress, and Ca2+ homeostasis. TSPO is highly expressed in steroidogenic tissues such as adrenal glands, but shows low expression in the central nervous system. During various disease states such as inflammation, neurodegeneration or cancer, the expression of mitochondrial TSPO in affected tissues is upregulated. The expression of TSPO can be traced for diagnostic purpose by high affinity radio-ligands. Moreover, the function of TSPO is modulated by synthetic as well as endogenous ligands with agonistic or antagonistic properties. Thus, TSPO ligands serve functions as both important biomarkers and putative therapeutic agents. In the present study, we aimed to characterize the effects of TSPO ligands on mouse BV-2 microglia cells, which express significant levels of TSPO, and analyzed the effect of XBD173, PK11195, and Ro5-4864, as well as the inflammatory reagent Lipopolysaccharides (LPS) on neurosteroid synthesis and on basic mitochondrial functions such as oxidative phosphorylation, mitochondrial membrane potential and Ca2+ homeostasis. Specific TSPO-dependent effects were separated from off-target effects by comparing lentiviral TSPO knockdown with shRNA scramble-controls and wild-type BV-2 cells. Our data demonstrate ligand-specific effects on different cellular functions in a TSPO-dependent or independent manner, providing evidence for both specific TSPO-mediated, as well as off-target effects.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN 18 KDA; DEPENDENT ANION CHANNEL; TRANSLOCATOR PROTEIN; BENZODIAZEPINE-RECEPTOR; NEURODEGENERATIVE DISEASES; THERAPEUTIC TARGET; RESIDENCE TIME; RO 5-4864; CA2+; NEUROPROTECTION; Translocator protein; Mitochondria; Steroid synthesis; Pregnenolone; Mitochondrial membrane potential; Mitochondrial respiration; Cytosolic Ca2+ level; Proliferation; Lentiviral knockdown |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 09:29 |
| Last Modified: | 01 Apr 2020 09:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26578 |
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