Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis.

Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis. Research Abstract Details 

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Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis. Abstract Text:

Natalia A Belikova,Jianfei Jiang,Yulia Y Tyurina,Qing Zhao,Michael W Epperly,Joel Greenberger,Valerian E Kagan,

PURPOSE: To determine whether cytochrome c (cyt c) content and associated cardiolipin oxidation can be determinants of cell sensitivity to irradiation-induced apoptosis. METHODS AND MATERIALS: The small interfering RNA (siRNA) approach was used to engineer HeLa cells with lowered contents of cyt c (14%, HeLa 1.2 cells). Cells were treated by gamma-irradiation (in doses of 5-40 Gy). Lipid oxidation was characterized by electrospray ionization mass spectrometry analysis and fluorescence high-performance liquid chromatography-based Amplex Red assay. Release of a proapoptotic factor (cyt c, Smac/DIABLO) was detected by Western blotting. Apoptosis was revealed by caspase-3/7 activation and phosphatidylserine externalization. RESULTS: Irradiation caused selective accumulation of hydroperoxides in cardiolipin (CL) but not in other phospholipids. HeLa 1.2 cells responded by a lower irradiation-induced accumulation of CL oxidation products than parental HeLa cells. Proportionally decreased release of a proapoptotic factor, Smac/DIABLO, was detected in cyt c-deficient cells after irradiation. Caspase-3/7 activation and phosphatidylserine externalization were proportional to the cyt c content in cells. CONCLUSIONS: Cytochrome c is an important catalyst of CL peroxidation, critical to the execution of the apoptotic program. This new role of cyt c in irradiation-induced apoptosis is essential for the development of new radioprotectors and radiosensitizers.

Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis. Publishing Authors By Initials

NA Belikova,J Jiang,YY Tyurina,Q Zhao,MW Epperly,J Greenberger,VE Kagan,

For similar peptides: intracellular signaling peptides and proteins: apoptosis regulatory proteins: proto-oncogene proteins c-bcl-2: bcl-2-associated x protein research abstracts see: peptides: intracellular signaling peptides and proteins: apoptosis regulatory proteins: proto-oncogene proteins c-bcl-2: bcl-2-associated x protein research

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Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: International journal of radiation oncology, biolo

VOLUME: 69

Page Numbers: 176-86

Journal Abbreviation: Int. J. Radiat. Oncol. Biol. P

ISSN: 0360-3016

DAY: 1

MONTH: Sep

YEAR: 2007

Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7603616

Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis. Keywords Mesh Terms:

KEYWORDS: bcl-2-Associated X Protein

MESH TERMS: metabolism

Chemical & Substance for Abstract: Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis. Information

Substance Name: Caspase 7

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Cardiolipin-specific peroxidase reactions of cytochrome C in mitochondria during irradiation-induced apoptosis.

AFFILIATION: Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.

Country: United States

AGENCY: United States NIAID

GRANT: U19 AI068021

ACRONYM: AI

MEDLINETA: Int J Radiat Oncol Biol Phys

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