Up-regulation of mitochondrial peripheral benzodiazepine receptor expression by tumor necrosis factor alpha in testicular Leydig cells
Abstract
Porcine Leydig cells in primary cultures are resistant to tumor necrosis factor alpha (TNFalpha) cytotoxicity. Here we report that these cells can be rendered sensitive to TNFalpha killing by treatment with the translational inhibitor cycloheximide, suggesting the existence of proteins that can suppress the death stimulus induced by the cytokine. In search of these cytoprotective proteins, we focused on the constituents of the mitochondrial permeability transition pore (PT pore), whose opening has been shown to play a critical role in the TNFalpha-mediated death pathway. We found that TNFalpha up-regulated mRNA and protein expression of the mitochondrial peripheral benzodiazepine receptor (PBR), an outer membrane-derived constituent of the pore. A strong correlation was established between the resistance of the cells to TNFalpha killing and the density of PBR-binding sites. Concomitantly, TNFalpha down-regulated Bcl-2 mRNA and protein expression. As Bcl-2 has been shown to be an endogenous inhibitor of the PT pore, we hypothesize that the TNFalpha-induced up-regulation of PBR expression may compensate for the decrease in Bcl-2 levels to prevent the opening of the PT pore.
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Inflammatory cytokines such as interleukin-1β, tumour necrosis factor-α and interferon-γ have been shown to increase levels of TSPO in various cell types, including astrocytes.
“inflammatory cytokines such as interleukin-1β, tumour necrosis factor-α and interferon-γ have been shown to increase levels of TSPO in various cell types, including astrocytes [62–65]”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [62]
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- Authors
- Rey, C., Mauduit, C., Naureils, O., Benahmed, M., Louisot, P., & Gasnier, F.
- Affiliations
- Inserm (FR)
- Corresponding author
- Gasnier, Françoise
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 60
- Issue
- 11
- Pages
- 1639-1646
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W175293464
- Cited by
- 36
- References
- 50
- Citations by year
- 2026: 1 · 2022: 1 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 2 · 2012: 2
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- TNF-α, mitochondrial permeability transition pore, Bcl-2, cycloheximide, cytoprotection, apoptosis
- MeSH terms
- Animals, Antifungal Agents, Antineoplastic Agents, Binding Sites, Cell Survival, Cycloheximide, Isoquinolines, Leydig Cells, Male, Mitochondria, Receptors, GABA-A, RNA, Messenger, Swine, Testis, Tritium, Tumor Necrosis Factor-alpha, Up-Regulation, Gene Expression, Proto-Oncogene Proteins c-bcl-2, In Vitro Techniques
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