ArticleCardiovascular toxicology2008
Cardiac-targeted transgenic mutant mitochondrial enzymes: mtDNA defects, antiretroviral toxicity and cardiomyopathy.
Article in Cardiovascular toxicology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Inherited mitochondrial genomic instability and chemical exposures.Toxicology · 2017Review
- Maintaining ancient organelles: mitochondrial biogenesis and maturation.Circulation research · 2015Review
- Long-term exposure of mice to nucleoside analogues disrupts mitochondrial DNA maintenance in cortical neurons.PloS one · 2014Article
- Thymidine kinase and mtDNA depletion in human cardiomyopathy: epigenetic and translational evidence for energy starvation.Physiological genomics · 2013Article
- Detection of differentially methylated gene promoters in failing and nonfailing human left ventricle myocardium using computation analysis.Physiological genomics · 2013Article
- Transgenic mouse model with deficient mitochondrial polymerase exhibits reduced state IV respiration and enhanced cardiac fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2013Article
- Mouse Models of Oxidative Stress Indicate a Role for Modulating Healthy Aging.Journal of clinical & experimental pathology · 2012Article
- The role of transporters in the toxicity of nucleoside and nucleotide analogs.Expert opinion on drug metabolism & toxicology · 2012Review
- Absence of mitochondrial toxicity in hearts of transgenic mice treated with abacavir.Cardiovascular toxicology · 2010Article
- Long-term AZT exposure alters the metabolic capacity of cultured human lymphoblastoid cells.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
- Transgenic cardiac-targeted overexpression of human thymidylate kinase.Laboratory investigation; a journal of technical methods and pathology · 2010Article
- Tenofovir renal toxicity targets mitochondria of renal proximal tubules.Laboratory investigation; a journal of technical methods and pathology · 2009Article
- Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation.Laboratory investigation; a journal of technical methods and pathology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitochondrial (mt) DNA biogenesis is critical to cardiac contractility. DNA polymerase gamma (Pol gamma) replicates mtDNA, whereas thymidine kinase 2 (TK2) monophosphorylates pyrimidines intramitochondrially. Point mutations in POLG and TK2 result in clinical diseases associated with mtDNA depletion and organ dysfunction. Pyrimidine analogs (NRTIs) inhibit Pol gamma and mtDNA replication. Cardiac "dominant negative" murine transgenes (TGs; Pol gamma Y955C, and TK2 H121N or I212N) defined the role of each in the heart. mtDNA abundance, histopathological features, histochemistry, mitochondrial protein abundance, morphometry, and echocardiography were determined for TGs in "2 x 2" studies with or without pyrimidine analogs. Cardiac mtDNA abundance decreased in Y955C TGs ( approximately 50%) but increased in H121N and I212N TGs (20-70%). Succinate dehydrogenase (SDH) increased in hearts of all mutants. Ultrastructural changes occurred in Y955C and H121N TGs. Histopathology demonstrated hypertrophy in H121N, LV dilation in I212N, and both hypertrophy and dilation in Y955C TGs. Antiretrovirals increased LV mass ( approximately 50%) for all three TGs which combined with dilation indicates cardiomyopathy. Taken together, these studies demonstrate three manifestations of cardiac dysfunction that depend on the nature of the specific mutation and antiretroviral treatment. Mutations in genes for mtDNA biogenesis increase risk for defective mtDNA replication, leading to LV hypertrophy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.