Detection of mitochondrial dysfunction by EPR technique in mouse model of dilated cardiomyopathy

被引：45

作者：

Elas, Martyna ^{[1
]}

Bielanska, Joanna ^{[1
]}

Pustelny, Katarzyna ^{[1
]}

Plonka, Przemyslaw M. ^{[1
]}

Drelicharz, Lukasz ^{[2
]}

Skorka, Tomasz ^{[3
]}

Tyrankiewicz, Urszula ^{[3
]}

Wozniak, Miroslaw ^{[2
]}

Heinze-Paluchowska, Sylwia ^{[3
]}

Walski, Michal ^{[4
]}

Wojnar, Leszek ^{[5
]}

Fortin, Dominique ^{[6
,7
]}

Ventura-Clapier, Renee ^{[6
,7
]}

Chlopicki, Stefan ^{[2
]}

机构：

[1] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Biophys, Lab Rodiospect Canc & Radiobiol, PL-30387 Krakow, Poland

[2] Jagiellonian Univ, Coll Med, Dept Expt Pharmacol, Chair Pharmacol, PL-31531 Krakow, Poland

[3] Polish Acad Sci, H Niewodniczanski Inst Nucl Phys, Krakow, Poland

[4] Polish Acad Sci, M Mossakowski Med Res Ctr, Warsaw, Poland

[5] Krakow Tech Univ, Inst Appl Comp Sci, PL-31155 Krakow, Poland

[6] INSERM, U 769, F-92296 Chatenay Malabry, France

[7] Univ Paris Sud, IFR 141, F-92296 Chatenay Malabry, France

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2008年 / 45卷 / 03期

关键词：

heart failure; mitochondria; EPR; semiquinones; iron;

D O I：

10.1016/j.freeradbiomed.2008.04.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Tg alpha q*44 mice with targeted overexpression of activated G alpha q protein in cardiomyocytes mimic many of the phenotypic characteristics of dilated cardiomyopathy in humans. However, it is not known whether the phenotype of Tg alpha q*44 mice would also involve dysfunction of cardiac mitochondria. The aim of the present work was to examine changes in EPR signals of semiquinones and iron in Fe-S clusters, as compared to classical biochemical indices of mitochondrial function in hearts from Tg alpha q*44 mice in relation to the progression of heart failure. Tg alpha q*44 mice at the age of 14 months displayed pulmonary congestion, increased heart/body ratio and impairment of cardiac function as measured in vivo by MRI. However, in hearts from Tg alpha q*44 mice already at the age of 10 months EPR signals of semiquinones, as well as cyt c oxidase activity were decreased, suggesting alterations in mitochondrial electron flow. Furthermore, in 14-months old Tg alpha q*44 mice loss of iron in Fe-S clusters, impaired citrate synthase activity, and altered mitochondrial ultrastructure were observed, supporting mitochondrial dysfunction in Tg alpha q*44 mice. In conclusion, the assessment of semiquinones content and Fe(III) analysis by EPR represents a rational approach to detect dysfunction of cardiac mitochondria. Decreased contents of semiquinones detected by EPR and a parallel decrease in cyt c oxidase activity occurs before hemodynamic decompensation of heart failure in Tg alpha q*44 mice suggesting that alterations in function of cardiac mitochondria contribute to the development of the overt heart failure in this model. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：321 / 328

页数：8

共 50 条

[1]

Abe H, 1983, Adv Myocardiol, V4, P107

[2]

AISEN P, 1978, J BIOL CHEM, V253, P1930

[3]

MYOCARDIAL ISCHEMIA AND REPERFUSION - DIRECT EVIDENCE FOR FREE-RADICAL GENERATION BY ELECTRON-SPIN RESONANCE SPECTROSCOPY [J].