Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis

Inoue, Takahiro; Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Matsuo, Yosuke; Arai, Shinobu; Saku, Keita; Sunagawa, Kenji

doi:10.1152/ajpheart.00044.2016

Cited by 24 publications

(19 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decrease in mitochondrial biogenesis is a key component of the development of heart failure after MI [41]. It has been reported that mitochondrial biogenesis was severely impaired in MI and that the preservation of mtDNA copy number alleviated impaired mitochondrial biogenesis [42]. Our results showed that NBP-treatment could protect mitochondrial function in H9c2 cells exposed to oxidative stress.…”

Section: Discussionsupporting

confidence: 55%

Dl-3-n-butylphthalide protects the heart against ischemic injury and H9c2 cardiomyoblasts against oxidative stress: involvement of mitochondrial function and biogenesis

Tian

Yang

et al. 2017

J Biomed Sci

View full text Add to dashboard Cite

BackgroundMyocardial infarction (MI) is an acute and fatal condition that threatens human health. Dl-3-n-butylphthalide (NBP) has been used for the treatment of acute ischemic stroke. Mitochondria may play a protective role in MI injury. However, there are few reports on the cardioprotective effect of NBP or the potential mitochondrial mechanism for the NBP-induced protection against cardiac ischemia injury. We investigated the therapeutic effects of NBP in an in vivo MI model and an in vitro oxidative stress model, as well as the potential mitochondrial mechanism.MethodsThis study comprised two different experiments. The aim of experiment 1 was to determine the protective effects of NBP on MI and the underlying mechanisms in vivo. In part 1, myocardial infarct size was measured by staining with 2,3,5-triphenyltetrazoliumchloride (TTC). Myocardial enzymes and mitochondrial enzymes were assayed. The aim of experiment 2 was to investigate the role of NBP in H2O2-induced myocardial ischemic injury in H9c2 cells and to determine the potential mechanism. In part 2, H9c2 cell viability was evaluated. ROS levels, mitochondrial morphology, and mitochondrial membrane potential of H9c2 cells were measured. ATP levels were evaluated using an assay kit; mitochondrial DNA (mtDNA), the expressions of NRF-1 and TFAM, and mitochondrial biogenesis factors were determined.ResultsNBP treatment significantly reduced the infarct ratio, as observed by TTC staining, decreased serum myocardial enzymes in MI, and restored heart mitochondrial enzymes (isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and a-ketoglutarate dehydrogenase (a-KGDH) activities after MI. Moreover, in in vitro studies, NBP significantly increased the viability of H9c2 cells in a dose-dependent manner, reduced cell apoptosis, protected mitochondrial functions, elevated the cellular ATP levels, and promoted H2O2-induced mitochondrial biogenesis in H9c2 cardiomyoblasts.ConclusionCollectively, the results from both the in vivo and in vitro experiments suggested that NBP exerted a cardioprotective effect on cardiac ischemic injury via the regulation of mitochondrial function and biogenesis.

show abstract

Section: Discussionsupporting

confidence: 55%

Dl-3-n-butylphthalide protects the heart against ischemic injury and H9c2 cardiomyoblasts against oxidative stress: involvement of mitochondrial function and biogenesis

Tian

Yang

et al. 2017

J Biomed Sci

View full text Add to dashboard Cite

show abstract

“…Earlier studies have demonstrated that helicase overexpression increases mtDNA copy number ( 19 , 22 ) and provides beneficial effects in various pathological conditions ( 25–27 , 55 ). The latter may relate directly to the complex structure of human mtDNA found in heart muscle, in which a substantial fraction is found as catenated multimers that accumulate with age ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Structural rearrangements in the mitochondrial genome of Drosophila melanogaster induced by elevated levels of the replicative DNA helicase

Ciesielski

Nadalutti

Oliveira

et al. 2018

Nucleic Acids Research

View full text Add to dashboard Cite

Pathological conditions impairing functions of mitochondria often lead to compensatory upregulation of the mitochondrial DNA (mtDNA) replisome machinery, and the replicative DNA helicase appears to be a key factor in regulating mtDNA copy number. Moreover, mtDNA helicase mutations have been associated with structural rearrangements of the mitochondrial genome. To evaluate the effects of elevated levels of the mtDNA helicase on the integrity and replication of the mitochondrial genome, we overexpressed the helicase in Drosophila melanogaster Schneider cells and analyzed the mtDNA by two-dimensional neutral agarose gel electrophoresis and electron microscopy. We found that elevation of mtDNA helicase levels increases the quantity of replication intermediates and alleviates pausing at the replication slow zones. Though we did not observe a concomitant alteration in mtDNA copy number, we observed deletions specific to the segment of repeated elements in the immediate vicinity of the origin of replication, and an accumulation of species characteristic of replication fork stalling. We also found elevated levels of RNA that are retained in the replication intermediates. Together, our results suggest that upregulation of mtDNA helicase promotes the process of mtDNA replication but also results in genome destabilization.

show abstract

“…To evaluate the current reporting of echocardiographic results, we accessed PubMed on July 21, 2017, and searched for “mouse and American Journal of Physiology and (echocardiography or echocardiographic or ultrasound).” This search resulted in 437 articles, of which 52 articles were published between January 1, 2016, and present as well as 14 articles that were excluded as false positives (two kidney, one liver, one lung, one bone, one RV, two rat not mouse, one fetal not adult, and five with no cardiac echocardiography results). The remaining 38 articles were analyzed both for completeness of information provided and for quality assessment of the echocardiography values reported ( 11 , 13 , 22 , 27 , 30 , 36 , 38 , 39 , 42 , 45 , 52 , 54 , 57 , 59 , 65 , 70 , 75 , 76 , 78 , 85 , 102 , 114 , 117 – 119 , 132 , 147 , 148 , 158 , 160 , 165 , 170 , 172 , 182 , 187 , 193 , 201 , 206 ).…”

Section: Echocardiographymentioning

confidence: 99%

Guidelines for measuring cardiac physiology in mice

Lindsey

Kassiri

Virag

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

264

194

View full text Add to dashboard Cite

Cardiovascular disease is a leading cause of death, and translational research is needed to understand better mechanisms whereby the left ventricle responds to injury. Mouse models of heart disease have provided valuable insights into mechanisms that occur during cardiac aging and in response to a variety of pathologies. The assessment of cardiovascular physiological responses to injury or insult is an important and necessary component of this research. With increasing consideration for rigor and reproducibility, the goal of this guidelines review is to provide best-practice information regarding how to measure accurately cardiac physiology in animal models. In this article, we define guidelines for the measurement of cardiac physiology in mice, as the most commonly used animal model in cardiovascular research.Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/guidelines-for-measuring-cardiac-physiology-in-mice/.

show abstract

Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis

Abstract: Inoue T, Ikeda M, Ide T, Fujino T, Matsuo Y, Arai S, Saku K, Sunagawa K. Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis.

Cited by 24 publications

References 45 publications

Dl-3-n-butylphthalide protects the heart against ischemic injury and H9c2 cardiomyoblasts against oxidative stress: involvement of mitochondrial function and biogenesis

Dl-3-n-butylphthalide protects the heart against ischemic injury and H9c2 cardiomyoblasts against oxidative stress: involvement of mitochondrial function and biogenesis

Structural rearrangements in the mitochondrial genome of Drosophila melanogaster induced by elevated levels of the replicative DNA helicase

Guidelines for measuring cardiac physiology in mice

Contact Info

Product

Resources

About