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Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria.

Publication ,  Journal Article
Spasojević, I; Chen, Y; Noel, TJ; Yu, Y; Cole, MP; Zhang, L; Zhao, Y; St Clair, DK; Batinić-Haberle, I
Published in: Free Radic Biol Med
April 15, 2007

The Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnIIITE-2-PyP5+ (AEOL-10113) has proven effective in treating oxidative stress-induced conditions including cancer, radiation damage, diabetes, and central nervous system trauma. The ortho cationic pyridyl nitrogens of MnTE-2-PyP5+ are essential for its high antioxidant potency. The exceptional ability of MnIIITE-2-PyP5+ to dismute O2.- parallels its ability to reduce ONOO- and CO3-. Decreasing levels of these species are considered its predominant mode of action, which may also involve redox regulation of signaling pathways. Recently, Ferrer-Sueta at al. (Free Radic. Biol. Med. 41:503-512; 2006) showed, with submitochondrial particles, that>or=3 microM MnIIITE-2-PyP5+ was able to protect components of the mitochondrial electron transport chain from peroxynitrite-mediated damage. Our study complements their data in showing, for the first time that micromolar mitochondrial concentrations of MnIIITE-2-PyP5+ are obtainable in vivo. For this study we have developed a new and sensitive method for MnIIITE-2-PyP5+ determination in tissues. The method is based on the exchange of porphyrin Mn2+ with Zn2+, followed by the HPLC/fluorescence detection of ZnIITE-2-PyP4+. At 4 and 7 h after a single 10 mg/kg intraperitoneal administration of MnIIITE-2-PyP5+, the mice (8 in total) were anesthetized and perfused with saline. Mitochondria were then isolated by the method of Mela and Seitz (Methods Enzymol.55:39-46; 1979). We found MnIIITE-2-PyP5+ localized in heart mitochondria to 2.95 ng/mg protein. Given the average value of mitochondrial volume of 0.6 microL/mg protein, the calculated MnIIITE-2-PyP5+ concentration is 5.1 microM, which is sufficient to protect mitochondria from oxidative damage. This study establishes, for the first time, that MnIIITE-2-PyP5+, a highly charged metalloporphyrin, is capable of entering mitochondria in vivo at levels sufficient to exert there its antioxidant action; such a result encourages its development as a prospective therapeutic agent.

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Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

April 15, 2007

Volume

42

Issue

8

Start / End Page

1193 / 1200

Location

United States

Related Subject Headings

  • Zinc
  • Superoxide Dismutase
  • Spectrophotometry
  • Models, Molecular
  • Mitochondria, Heart
  • Mice
  • Metalloporphyrins
  • Manganese
  • Biochemistry & Molecular Biology
  • Antioxidants
 

Citation

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Spasojević, I., Chen, Y., Noel, T. J., Yu, Y., Cole, M. P., Zhang, L., … Batinić-Haberle, I. (2007). Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria. Free Radic Biol Med, 42(8), 1193–1200. https://doi.org/10.1016/j.freeradbiomed.2007.01.019
Spasojević, Ivan, Yumin Chen, Teresa J. Noel, Yiqun Yu, Marsha P. Cole, Lichun Zhang, Yunfeng Zhao, Daret K. St Clair, and Ines Batinić-Haberle. “Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria.Free Radic Biol Med 42, no. 8 (April 15, 2007): 1193–1200. https://doi.org/10.1016/j.freeradbiomed.2007.01.019.
Spasojević I, Chen Y, Noel TJ, Yu Y, Cole MP, Zhang L, et al. Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria. Free Radic Biol Med. 2007 Apr 15;42(8):1193–200.
Spasojević, Ivan, et al. “Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria.Free Radic Biol Med, vol. 42, no. 8, Apr. 2007, pp. 1193–200. Pubmed, doi:10.1016/j.freeradbiomed.2007.01.019.
Spasojević I, Chen Y, Noel TJ, Yu Y, Cole MP, Zhang L, Zhao Y, St Clair DK, Batinić-Haberle I. Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria. Free Radic Biol Med. 2007 Apr 15;42(8):1193–1200.
Journal cover image

Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

April 15, 2007

Volume

42

Issue

8

Start / End Page

1193 / 1200

Location

United States

Related Subject Headings

  • Zinc
  • Superoxide Dismutase
  • Spectrophotometry
  • Models, Molecular
  • Mitochondria, Heart
  • Mice
  • Metalloporphyrins
  • Manganese
  • Biochemistry & Molecular Biology
  • Antioxidants