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Cell surface expression of heat shock proteins in dog neutrophils induced by mitochondrial benzodiazepine receptor ligands

Abstract:

The effect of peripheral-type benzodiazepines on dog neutrophil stimulation was studied. Ro 5-4864 (a specific ligand of mitochondrial benzodiazepine receptor) and diazepam (which binds both to mitochondrial and central benzodiazepine receptors) did not show any direct toxic effect against neutrophils. PK 11195, a putative antagonist of the mitochondrial benzodiazepine receptor and an isoquinoline derivative, had a direct toxic effect at a concentration of 5 × 10-5 M (72% of cells were viable). Ro 5-4864 (10-6-10-4 M) and diazepam (10-6-2.5 × 10-4M) induced an intracellular oxidative stress in dog neutrophils. These compounds, in a micromolar range, also induced a concentration-dependent cell surface expression of heat shock protein (HSP) families. The percentages of positive cells that express these proteins were: 76.2% for HSP 27 kDa; 54.3% for HSP 72 kDa and 69.6% for HSP 90 kDa for Ro 5-4864 (10-4 M), and 66.7% for HSP 27 kDa; 45.4% for HSP 72 kDa and 78.3 for HSP 90 kDa for diazepam (2.5 × 10-4 M). It appears that this HSP expression, induced by peripheral-type benzodiazepines could be mediated by an intracellular oxidative stress. © 1995 Elsevier Science B.V. All rights reserved.