Cytokine-induced apoptosis and necrosis are preceded by disruption of the mitochondrial membrane potential (Deltapsi(m)) in pancreatic RINm5F cells: prevention by Bcl-2.

Abstract

The mechanisms of cytokine-induced beta-cell death are poorly characterised. In rat insulin-producing RINm5F cells, the combination of interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha presently induced disruption of the mitochondrial membrane potential (Deltapsi(m)) as demonstrated by reduced JC-1 fluorescence. The reduction of Deltapsi(m) was maximal after 8 h and was preceded by increased formation of reactive oxygen species (ROS), as assessed by dichlorofluorescein-diacetate (DCFH-DA) fluorescence. A nitric oxide synthase-, but not a ROS-inhibitor, prevented cytokine-induced loss of Deltapsi(m). Overexpression of the anti-apoptotic protein Bcl-2 increased both JC-1 and DCFH-DA fluorescence, which was paralleled by protection against cytokine-induced apoptosis and necrosis. It is concluded that cytokines induce a nitric oxide-dependent disruption of Deltapsi(m) and that this may be a necessary event for both beta-cell apoptosis and necrosis. Bcl-2 may prevent beta-cell death by counteracting mitochondrial permeability transition.

• Authors: Andreea Barbu, Nils Welsh, Johan Saldeen
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 190 Issue 1-2 Pg. 75-82 (Apr 25 2002) ISSN: 0303-7207 [Print] Ireland
• PMID: 11997180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Carbocyanines
• Enzyme Inhibitors
• Fluoresceins
• Fluorescent Dyes
• Interleukin-1
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• diacetyldichlorofluorescein
• 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine
• Interferon-gamma
• Catalase
• Nitric Oxide Synthase

Topics

• Animals
• Apoptosis
• Benzimidazoles (metabolism)
• Carbocyanines (metabolism)
• Catalase (metabolism)
• Cell Line
• Enzyme Inhibitors (pharmacology)
• Flow Cytometry (methods)
• Fluoresceins (metabolism)
• Fluorescent Dyes (metabolism)
• Interferon-gamma (pharmacology)
• Interleukin-1 (pharmacology)
• Islets of Langerhans (drug effects, physiology)
• Membrane Potentials (drug effects)
• Mitochondria (drug effects, metabolism)
• Necrosis
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)