Transgenic mouse model with deficient mitochondrial polymerase exhibits reduced state IV respiration and enhanced cardiac fibrosis

Laboratory Investigation

Volumn 93, Issue 2, 2013, Pages 151-158

  Koczor, Christopher A ^a   Torres, Rebecca A ^a   Fields, Earl ^a   Qin, Qianhong ^a   Park, Jade ^a   Ludaway, Tomika ^a   Russ, Rodney ^a   Lewis, William ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

cardiac fibrosis; heart; mitochondrial DNA; polymerase gamma

Indexed keywords

DNA DIRECTED DNA POLYMERASE GAMMA; MITOCHONDRIAL DNA; ZIDOVUDINE;

ARTICLE; CONGESTIVE CARDIOMYOPATHY; DISEASE COURSE; HEART FAILURE; HEART LEFT VENTRICLE VOLUME; HEART MUSCLE FIBROSIS; HEART VENTRICLE ENDDIASTOLIC PRESSURE; HISTOPATHOLOGY; MITOCHONDRIAL RESPIRATION; MOLECULAR PATHOLOGY; MOUSE; MUTANT; NONHUMAN; PRIORITY JOURNAL; RESPIRATORY CHAIN; TRANSGENIC MOUSE; WILD TYPE;

ANALYSIS OF VARIANCE; ANIMALS; CROSSES, GENETIC; DISEASE MODELS, ANIMAL; DNA PRIMERS; DNA, MITOCHONDRIAL; DNA-DIRECTED DNA POLYMERASE; ECHOCARDIOGRAPHY; ENDOMYOCARDIAL FIBROSIS; GENOTYPE; HISTOLOGICAL TECHNIQUES; HYDROXYPROLINE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MITOCHONDRIAL DISEASES; MUTATION, MISSENSE; MYOCARDIAL CONTRACTION; OXIMETRY; RESPIRATORY PHYSIOLOGICAL PROCESSES; ZIDOVUDINE;

EID: 84873838183     PISSN: 00236837     EISSN: 15300307     Source Type: Journal    
DOI: 10.1038/labinvest.2012.146     Document Type: Article

References (28)

1. Neubauer S. The failing heart-an engine out of fuel. N Engl J Med 2007;356:1140-1151.
2. Kohler JJ, Hosseini SH, Green E, et al. Cardiac-targeted transgenic mutant mitochondrial enzymes: mtDNA defects, antiretroviral toxicity and cardiomyopathy. Cardiovasc Toxicol 2008;8:57-69.
3. Lewis W, Day BJ, Kohler JJ, et al. Decreased mtDNA, oxidative stress, cardiomyopathy, and death from transgenic cardiac targeted human mutant polymerase gamma. Lab Invest 2007;87:326-335.
4. Kohler JJ, Hosseini SH, Lewis W, et al. Mitochondrial DNA impairment in nucleoside reverse transcriptase inhibitor-associated cardiomyopathy. Chem Res Toxicol 2008;21:990-996.
5. Karamanlidis G, Nascimben L, Couper GS, et al. Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res 2010;106:1541-1548.
6. Lewis W, Kohler JJ, Hosseini SH, et al. Antiretroviral nucleosides, deoxynucleotide carrier and mitochondrial DNA: evidence supporting the DNA pol gamma hypothesis. AIDS 2006;20:675-684.
7. Lewis W, Day BJ, Copeland WC. Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective. Nat Rev Drug Discov 2003;2:812-822.
8. Koczor CA, Torres RA, Lewis W. The role of transporters in the toxicity of nucleoside and nucleotide analogs. Expert Opin Drug Metab Toxicol 2012;8:665-676.
9. Kohler JJ, Hosseini SH, Cucoranu I, et al. Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Lab Invest 2009;89:122-130.
10. Purevjav E, Nelson DP, Varela JJ, et al. Myocardial Fas ligand expression increases susceptibility to AZT-induced cardiomyopathy. Cardiovasc Toxicol 2007;7:255-263.
11. Friis-Moller N, Thiebaut R, Reiss P, et al. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil 2010;17:491-501.
12. Lewis W, Haase CP, Raidel SM, et al. Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice. Lab Invest 2001;81:1527-1536.
13. Estep PA, Johnson KA. Effect of the Y955C mutation on mitochondrial DNA polymerase nucleotide incorporation efficiency and fidelity. Biochemistry 2011;50:6376-6386.
14. Graziewicz MA, Bienstock RJ, Copeland WC. The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-20-deoxyguanosine. Hum Mol Genet 2007;16: 2729-2739.
15. Copeland WC, Ponamarev MV, Nguyen D, et al. Mutations in DNA polymerase gamma cause error prone DNA synthesis in human mitochondrial disorders. Acta Biochim Pol 2003;50:155-167.
16. Woessner Jr. JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 1961;93:440-447.
17. Starcher B. A ninhydrin-based assay to quantitate the total protein content of tissue samples. Anal Biochem 2001;292:125-129.
18. Faulx MD, Ernsberger P, Vatner D, et al. Strain-dependent betaadrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice. Am J Physiol Heart Circ Physiol 2005;289:H30-H36.
19. Kania G, Blyszczuk P, Eriksson U. Mechanisms of cardiac fibrosis in inflammatory heart disease. Trends Cardiovasc Med 2009;19:247-252.
20. Zannad F, Dousset B, Alla F. Treatment of congestive heart failure: interfering the aldosterone-cardiac extracellular matrix relationship. Hypertension 2001;38:1227-1232.
21. Dai DF, Chen T, Szeto H, et al. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol 2011;58:73-82.
22. Narula N, Zaragoza MV, Sengupta PP, et al. Adenine nucleotide translocase 1 deficiency results in dilated cardiomyopathy with defects in myocardial mechanics, histopathological alterations, and activation of apoptosis. JACC Cardiovasc Imaging 2011;4:1-10.
23. Dai DF, Rabinovitch PS, Ungvari Z. Mitochondria and cardiovascular aging. Circ Res 2012;110:1109-1124.
24. Atanassova N, Fuste JM, Wanrooij S, et al. Sequence-specific stalling of DNA polymerase gamma and the effects of mutations causing progressive ophthalmoplegia. Hum Mol Genet 2011;20:1212-1223.
25. Graziewicz MA, Longley MJ, Bienstock RJ, et al. Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia. Nat Struct Mol Biol 2004;11:770-776.
26. Hosseini SH, Kohler JJ, Haase CP, et al. Targeted transgenic overexpression of mitochondrial thymidine kinase (TK2) alters mitochondrial DNA (mtDNA) and mitochondrial polypeptide abundance: transgenic TK2, mtDNA, and antiretrovirals. Am J Pathol 2007; 170:865-874.
27. Koczor CA, Lewis W. Nucleoside reverse transcriptase inhibitor toxicity and mitochondrial DNA. Expert Opin Drug Metab Toxicol 2010;6: 1493-1504.
28. Kohler JJ, Cucoranu I, Fields E, et al. Transgenic mitochondrial superoxide dismutase and mitochondrially targeted catalase prevent antiretroviral-induced oxidative stress and cardiomyopathy. Lab Invest 2009;89:782-790.