Mitochondria-targeted antioxidant SkQ1 (10-(6′-plastoquinonyl)decyltriphenylphosphonium bromide) inhibits mast cell degranulation in vivo and in vitro

Abstract

The therapeutic effect of mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium bromide (SkQ1) in experimental models of acute inflammation and wound repair has been shown earlier. It was suggested that the antiinflammatory activity of SkQ1 is related to its ability to suppress inflammatory activation of the vascular endothelium and neutrophil migration into tissues. Here, we demonstrated that SkQ1 inhibits activation of mast cells (MCs) followed by their degranulation and histamine release in vivo and in vitro. Intraperitoneal injections of SkQ1 in the mouse air-pouch model reduced the number of leukocytes in the air-pouch cavity and significantly decreased the histamine content in it, as well as suppressing MC degranulation in the air-pouch tissue. The direct effect of SkQ1 on MCs was studied in vitro in the rat basophilic leukemia RBL-2H3 cell line. SkQ1 inhibited induced degranulation of RBL-2H3 cells. These results suggest that mitochondrial reactive oxygen species are involved in the activation of MCs. It is known that MCs play a crucial role in regulation of vascular permeability by secreting histamine. Suppression of MC degranulation by SkQ1 might be a significant factor in the antiinflammatory activity of this mitochondria-targeted antioxidant.

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Abbreviations

anti-DNP IgE:

mouse monoclonal IgE antibodies against dinitrophenol

DNP-BSA:

DNP-conjugated bovine serum albumin; MC, mast cell

mtROS:

mitochondrial ROS

PMA:

phorbol myristate acetate (phorbol ester)

RBL-2H3:

rat basophilic leukemia cell line

ROS:

reactive oxygen species

SkQ1:

10-(6′-plastoquinonyl)decyltriphenylphosphonium bromide

TGF-β1:

transforming growth factor β1

TNF:

tumor necrosis factor

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Correspondence to M. A. Chelombitko.

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Original Russian Text © M. A. Chelombitko, O. A. Averina, T. V. Vasilyeva, O. Yu. Pletiushkina, E. N. Popova, A. V. Fedorov, B. V. Chernyak, V. S. Shishkina, O. P. Ilinskaya, 2017, published in Biokhimiya, 2017, Vol. 82, No. 12, pp. 1858-1871.

Originally published in Biochemistry (Moscow) On-Line Papers in Press as Manuscript BM17-381, November 6, 2017.

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Chelombitko, M.A., Averina, O.A., Vasilyeva, T.V. et al. Mitochondria-targeted antioxidant SkQ1 (10-(6′-plastoquinonyl)decyltriphenylphosphonium bromide) inhibits mast cell degranulation in vivo and in vitro. Biochemistry Moscow 82, 1493–1503 (2017). https://doi.org/10.1134/S0006297917120082

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Keywords

  • inflammation
  • mast cell
  • degranulation
  • histamine
  • mitochondria-targeted antioxidant