1. Academic Validation
  2. Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis

Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis

  • Biochem Biophys Res Commun. 2016 Aug 5;476(4):600-606. doi: 10.1016/j.bbrc.2016.06.003.
Fumiya Ito 1 Takahiro Nishiyama 2 Lei Shi 1 Masahiko Mori 3 Tasuku Hirayama 4 Hideko Nagasawa 4 Hiroyuki Yasui 5 Shinya Toyokuni 6
Affiliations

Affiliations

  • 1 Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
  • 2 Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
  • 3 Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Department of Obstetrics and Genecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
  • 4 Laboratory of Pharmaceutical and Medical Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1113, Japan.
  • 5 Department of Analytical and Bionorganic Chemistry, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan.
  • 6 Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: toyokuni@med.nagoya-u.ac.jp.
Abstract

Iron is an essential nutrient for every type of life on earth. However, excess iron is cytotoxic and can lead to an increased Cancer risk in humans. Catalytic ferrous iron [Fe(II)] is an initiator of the Fenton reaction, which causes oxidative stress by generating hydroxyl radicals. Recently, it became possible to localize catalytic Fe(II) in situ with a turn-on fluorescent probe, RhoNox-1. Here, we screened each organ/cell of rats to globally evaluate the distribution of catalytic Fe(II) and found that eosinophils showed the highest abundance. In various cells, lysosomes were the major organelle, sharing ∼40-80% of RhoNox-1 fluorescence. We then used an ovalbumin-induced allergic peritonitis model to study the dynamics of catalytic Fe(II). Peritoneal lavage revealed that the total iron contents per cell were significantly decreased, whereas an increase in the number of inflammatory cells (macrophages, neutrophils, eosinophils and lymphocytes) resulted in an increased total iron content of the peritoneal inflammatory cells. Notably, macrophages, eosinophils and neutrophils exhibited significantly increased catalytic Fe(II) with increased DMT1 expression and decreased ferritin expression, though catalytic Fe(II) was significantly decreased in the peritoneal lavage fluid. In conclusion, catalytic Fe(II) in situ more directly reflects cellular activity and the accompanying pathology than total iron does.

Keywords

Catalytic (labile) ferrous iron; Fluorescent probe; Inflammation.

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