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Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide.

Publication ,  Journal Article
Charkoudian, LK; Dentchev, T; Lukinova, N; Wolkow, N; Dunaief, JL; Franz, KJ
Published in: Journal of inorganic biochemistry
December 2008

Dysregulation of localized iron homeostasis is implicated in several degenerative diseases, including Parkinson's, Alzheimer's, and age-related macular degeneration, wherein iron-mediated oxidative stress is hypothesized to contribute to cell death. Inhibiting toxic iron without altering normal metal-dependent processes presents significant challenges for standard small molecule chelating agents. We previously introduced BSIH (isonicotinic acid [2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene]-hydrazide) prochelators that are converted by hydrogen peroxide into SIH (salicylaldehyde isonicotinoyl hydrazone) chelating agents that inhibit iron-catalyzed hydroxyl radical generation. Here, we show that BSIH protects a cultured cell model for retinal pigment epithelium against cell death induced by hydrogen peroxide. BSIH is more stable than SIH in cell culture medium and is more protective during long-term experiments. Repetitive exposure of cells to BSIH is nontoxic, whereas SIH and desferrioxamine induce cell death after repeated exposure. Combined, our results indicate that cell protection by BSIH involves iron sequestration that occurs only when the cells are stressed by hydrogen peroxide. These findings suggest that prochelators discriminate toxic iron from healthy iron and are promising candidates for neuro- and retinal protection.

Duke Scholars

Published In

Journal of inorganic biochemistry

DOI

EISSN

1873-3344

ISSN

0162-0134

Publication Date

December 2008

Volume

102

Issue

12

Start / End Page

2130 / 2135

Related Subject Headings

  • Retinal Pigment Epithelium
  • Isonicotinic Acids
  • Iron
  • Inorganic & Nuclear Chemistry
  • Hydrogen Peroxide
  • Hydrazones
  • Humans
  • Cytoprotection
  • Cell Line
  • Boronic Acids
 

Citation

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Charkoudian, L. K., Dentchev, T., Lukinova, N., Wolkow, N., Dunaief, J. L., & Franz, K. J. (2008). Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide. Journal of Inorganic Biochemistry, 102(12), 2130–2135. https://doi.org/10.1016/j.jinorgbio.2008.08.001
Charkoudian, Louise K., Tzvete Dentchev, Nina Lukinova, Natalie Wolkow, Joshua L. Dunaief, and Katherine J. Franz. “Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide.Journal of Inorganic Biochemistry 102, no. 12 (December 2008): 2130–35. https://doi.org/10.1016/j.jinorgbio.2008.08.001.
Charkoudian LK, Dentchev T, Lukinova N, Wolkow N, Dunaief JL, Franz KJ. Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide. Journal of inorganic biochemistry. 2008 Dec;102(12):2130–5.
Charkoudian, Louise K., et al. “Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide.Journal of Inorganic Biochemistry, vol. 102, no. 12, Dec. 2008, pp. 2130–35. Epmc, doi:10.1016/j.jinorgbio.2008.08.001.
Charkoudian LK, Dentchev T, Lukinova N, Wolkow N, Dunaief JL, Franz KJ. Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide. Journal of inorganic biochemistry. 2008 Dec;102(12):2130–2135.
Journal cover image

Published In

Journal of inorganic biochemistry

DOI

EISSN

1873-3344

ISSN

0162-0134

Publication Date

December 2008

Volume

102

Issue

12

Start / End Page

2130 / 2135

Related Subject Headings

  • Retinal Pigment Epithelium
  • Isonicotinic Acids
  • Iron
  • Inorganic & Nuclear Chemistry
  • Hydrogen Peroxide
  • Hydrazones
  • Humans
  • Cytoprotection
  • Cell Line
  • Boronic Acids