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The mitochondria-targeted nitroxide JP4-039 augments potentially lethal irradiation damage repair

Rajagopalan, MS and Gupta, K and Epperly, MW and Franicola, D and Zhang, X and Wang, H and Zhao, H and Tyurin, VA and Pierce, JG and Kagan, VE and Wipf, P and Kanai, AJ and Greenberger, JS (2009) The mitochondria-targeted nitroxide JP4-039 augments potentially lethal irradiation damage repair. In Vivo, 23 (5). 717 - 726. ISSN 0258-851X

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Abstract

It was unknown if a mitochondria-targeted nitroxide (JP4-039) could augment potentially lethal damage repair (PLDR) of cells in quiescence. We evaluated 32D cl 3 murine hematopoietic progenitor cells which were irradiated and then either centrifugea to pellets (to simulate PLDR conditions) or left in exponential growth for 0, 24, 48 or 72 h. Pelleted cells demonstrated cell cycle arrest with a greater percentage in the G1-phase than did exponentially growing cells. Irradiation survival curves demonstrated a significant radiation damage mitigation effect of JP4-039 over untreated cells in cells pelleted for 24 h.No significant radiation mitigation was detected if drugs were added 48 or 72 h after irradiation. Electron paramagnetic resonance spectroscopy demonstrated a greater concentration of JP4-039 in mitochondria of 24 h-pelleted cells than in exponentially growing cells. These results establish a potential role of mitochondria-targeted nitroxide drugs as mitigators of radiation damage to quiescent cells including stem cells.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rajagopalan, MS
Gupta, K
Epperly, MW
Franicola, D
Zhang, Xxichen@pitt.eduXICHEN
Wang, Hhow8@pitt.eduHOW80000-0003-0477-2908
Zhao, H
Tyurin, VAvtyurin@pitt.eduVTYURIN
Pierce, JG
Kagan, VEkagan@pitt.eduKAGAN
Wipf, Ppwipf@pitt.eduPWIPF
Kanai, AJ
Greenberger, JSjoelg@pitt.eduJOELG
Date: 1 January 2009
Date Type: Publication
Journal or Publication Title: In Vivo
Volume: 23
Number: 5
Page Range: 717 - 726
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0258-851X
MeSH Headings: Animals; Antioxidants--pharmacology; Cell Cycle--drug effects; Cell Cycle--radiation effects; Cell Line; Cell Survival--drug effects; Hematopoietic Stem Cells--drug effects; Hematopoietic Stem Cells--pathology; Hematopoietic Stem Cells--radiation effects; Mice; Mice, Inbred C3H; Mitochondria--chemistry; Mitochondria--drug effects; Mitochondria--radiation effects; Nitrogen Oxides--analysis; Nitrogen Oxides--pharmacology; Radiation Injuries, Experimental--pathology; Radiation Injuries, Experimental--prevention & control; Radiation-Protective Agents--pharmacology
Other ID: NLM NIHMS210430, NLM PMC2899481
PubMed Central ID: PMC2899481
PubMed ID: 19779106
Date Deposited: 25 Jun 2013 15:44
Last Modified: 22 Jun 2021 13:56
URI: http://d-scholarship.pitt.edu/id/eprint/19095

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