Upregulation of mitochondrial peripheral benzodiazepine receptor expression by cytokine-induced damage of human pancreatic islets
Abstract
Cytokines produced by immune system cells infiltrating pancreatic islets are candidate mediators of islet beta-cell destruction in autoimmune insulin-dependent diabetes mellitus. After 72 h exposure of human pancreatic islets to a cytotoxic cytokine combination of interleukin 1 beta (50 U/ml), tumor necrosis factor alpha (1,000 U/ml), and interferon gamma (1,000 U/ml), an increase of cell death vs. control islets was demonstrated by TUNEL and cell death detection ELISA method. Islet death was associated with apoptosis and mitochondrial swelling as evidenced by electron microscopy. This effect was correlated with a marked decrease of Bcl-2 mRNA expression (without any major change of Bax mRNA) and a marked increase of inducible nitric oxide synthase mRNA. Since peripheral benzodiazepine receptors constitute the aspecific mitochondrial permeability transition pore, and that it has been suggested to be involved in cytokine-induced cell death, we evaluated the effects of the cytotoxic cytokines on PBR density and mRNA expression. We demonstrated that cytokine treatment of human islets induced an increase of maximum density of (3)H1-(2-chlorophenyl-N-methyl-1-methylpropyl)-3- isoquinolinecarboxamide binding sites, (5,110+/-193 vs. 3,421+/-336 fmol/mg proteins, P<0.05) with no significant change in the affinity constant value (9.45+/-0.869 vs. 8.7+/-1.159 nM). Moreover, an increase of the expression of peripheral benzodiazepine receptor mRNA was observed, suggesting an increased tr…
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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 [65]
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XIV LEGISLATURA – DISEGNI DI LEGGE E RELAZIONI - DOCUMENTI
Legge, D. D. (2010)
Role for the Peripheral Benzodiazepine Receptor in Neuroinflammation of Neurodegenerative disorders
Venneti, S. (2006) · D-Scholarship@Pitt (University of Pittsburgh)
Kaimal, S. B., & Paulose, C. S. (2005) · Dyuthi Digital Repository (Cochin University of Science and Technology)
- Authors
- Trincavelli, M. L., Marselli, L., Falleni, A., Gremigni, V., Ragge, E., Dotta, F., Santangelo, C., Marchetti, P., Lucacchini, A., & Martini, C.
- Affiliations
- University of Pisa (IT)
- Sapienza University of Rome (IT)
- ORCID
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2002-01
- Volume
- 84
- Issue
- 3
- Pages
- 636-644
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W2018862468
- Cited by
- 34
- References
- 43
- Citations by year
- 2024: 1 · 2022: 2 · 2020: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2012: 2
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- translocator protein (TSPO), mitochondrial permeability transition pore, pancreatic islets, beta-cell apoptosis, type 1 diabetes, IL-1β, TNF-α, interferon-gamma, Bcl-2, inducible nitric oxide synthase, mitochondrial swelling, receptor mRNA expression
- MeSH terms
- Adult, Cell Nucleus, Cells, Cultured, Humans, Interferon-gamma, Interleukin-1, Islets of Langerhans, Mitochondria, Receptors, GABA-A, RNA, Messenger, Tumor Necrosis Factor-alpha, Transcriptional Activation, Up-Regulation, Cytokines, Apoptosis, Nitric Oxide Synthase, Proto-Oncogene Proteins c-bcl-2, In Situ Nick-End Labeling, Nitric Oxide Synthase Type II
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