The heterozygous Sod2+/- mouse: modeling the mitochondrial role in drug toxicity

被引：23

作者：

Boelsterli, Urs A. ^{[1
]}

Hsiao, Chin-Ju J. ^{[1
]}

机构：

[1] Univ Connecticut, Dept Pharmaceut Sci, Sch Pharm, Storrs, CT 06269 USA

来源：

DRUG DISCOVERY TODAY | 2008年 / 13卷 / 21-22期

关键词：

D O I：

10.1016/j.drudis.2008.08.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Mitochondria have been increasingly implicated in being a crucial subcellular target and amplifying oxidative injury induced by many drugs. Among the major cytoprotective antioxidants is the mitochondrial matrix protein, superoxide dismutase-2 (SOD2). Genetic modification of the expression of SOD2 by transgenic techniques or gene silencing has generated a number of distinct animal models with SOD2 deficiency including the heterozygous Sod2(+/-) knockout mouse model. These mice display a discreet underlying mitochondrial stress but are otherwise phenotypically normal and thus model a variety of clinically silent mitochondrial abnormalities. The model has found application in oxidative stress and age-related research, but it is only recently that it has been successfully used to study mechanisms of idiosyncratic drug-induced liver injury.

引用

页码：982 / 988

页数：7

共 78 条

[31] Model mice for tissue-specific deletion of the manganese superoxide dismutase (MnSOD) gene [J].

Ikegami, T ;

Suzuki, Y ;

Shimizu, T ;

Isono, K ;

Koseki, H ;

Shirasawa, T .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 296 (03) :729-736

[32] Role of intracellular antioxidant enzymes after in vivo myocardial ischemia and reperfusion [J].

Jones, SP ;

Hoffmeyer, MR ;

Sharp, BR ;

Ho, YS ;

Lefer, DJ .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 284 (01) :H277-H282

[33] The developing use of heterozygous mutant mouse models in brain monoamine transporter research [J].

Kalueff, Allan V. ;

Ren-Patterson, Renee F. ;

Murphy, Dennis L. .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2007, 28 (03) :122-127

[34] Mitochondrial involvement in drug-induced hepatic injury [J].

Kass, George E. N. .

CHEMICO-BIOLOGICAL INTERACTIONS, 2006, 163 (1-2) :145-159

[35] Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis [J].

Kokoszka, JE ;

Coskun, P ;

Esposito, LA ;

Wallace, DC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2278-2283

[36] Mitochondrial membrane permeabilization in cell death [J].

Kroemer, Guido ;

Galluzzi, Lorenzo ;

Brenner, Catherine .

PHYSIOLOGICAL REVIEWS, 2007, 87 (01) :99-163

[37] Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen-induced liver injury [J].

Latchoumycandane, Calivarathan ;

Goh, Catherine W. ;

Ong, Michie M. K. ;

Boelsterli, Urs A. .

HEPATOLOGY, 2007, 45 (02) :412-421

[38] Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice [J].

Lebovitz, RM ;

Zhang, HJ ;

Vogel, H ;

Cartwright, J ;

Dionne, L ;

Lu, NF ;

Huang, S ;

Matzuk, MM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (18) :9782-9787

[39] Troglitazone-induced hepatic mitochondrial proteome expression dynamics in heterozygous Sod2+/- mice:: Two-stage oxidative injury [J].

Lee, Yie Hou ;

Chung, Maxey C. M. ;

Lin, Qingsong ;

Boelsterli, Urs A. .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2008, 231 (01) :43-51

[40] Proteomics profiling of hepatic mitochondria in heterozygous Sod2+/- mice, an animal model of discreet mitochondrial oxidative stress [J].

Lee, Yie Hou ;

Boelsterli, Urs A. ;

Lin, Qingsong ;

Chung, Maxey C. M. .

PROTEOMICS, 2008, 8 (03) :555-568

← 1 2 3 4 5 6 7 8 →