2. Academic Validation
  3. A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death

A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death

  • Nat Commun. 2011 Oct 11:2:497. doi: 10.1038/ncomms1499.
Jeffrey Atkinson 1,  Alexandr A Kapralov,  Naveena Yanamala,  Yulia Y Tyurina,  Andrew A Amoscato,  Linda Pearce,  Jim Peterson,  Zhentai Huang,  Jianfei Jiang,  Alejandro K Samhan-Arias,  Akihiro Maeda,  Weihong Feng,  Karla Wasserloos,  Natalia A Belikova,  Vladimir A Tyurin,  Hong Wang,  Jackie Fletcher,  Yongsheng Wang,  Irina I Vlasova,  Judith Klein-Seetharaman,  Detcho A Stoyanovsky,  Hülya Bayîr,  Bruce R Pitt,  Michael W Epperly,  Joel S Greenberger,  Valerian E Kagan
Affiliations

Affiliation

  • 1 Center for Free Radical and Antioxidant Health and Center for Medical Countermeasures against Radiation, University of Pittsburgh, Bridgeside Point, Pennsylvania 15219, USA.
PMID: 21988913 DOI: 10.1038/ncomms1499
Abstract

The risk of radionuclide release in terrorist acts or exposure of healthy tissue during radiotherapy demand potent radioprotectants/radiomitigators. Ionizing radiation induces cell death by initiating the selective peroxidation of cardiolipin in mitochondria by the peroxidase activity of its complex with cytochrome c leading to release of haemoprotein into the cytosol and commitment to the apoptotic program. Here we design and synthesize mitochondria-targeted triphenylphosphonium-conjugated imidazole-substituted oleic and stearic acids that blocked peroxidase activity of cytochrome c/cardiolipin complex by specifically binding to its haem-iron. We show that both compounds inhibit pro-apoptotic oxidative events, suppress cyt c release, prevent cell death, and protect mice against lethal doses of irradiation. Significant radioprotective/radiomitigative effects of imidazole-substituted oleic acid are observed after pretreatment of mice from 1 h before through 24 h after the irradiation.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z