Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Regulation And Role Of The Mitochondrial Transcription Factor In The Diabetic Rat Heart

Y. Nishio, A. Kanazawa, Yoshio Nagai, H. Inagaki, A. Kashiwagi
Published 2004 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Abstract: To clarify the mechanism of abnormalities in mitochondrial expression and function in diabetic rat heart, we have studied the transcriptional activities of mitochondrial DNA using isolated intact mitochondria from the heart of either diabetic or control rats. The transcriptional activity of cardiac mitochondria isolated from diabetic rats decreased to 40% of the control level (P < 0.01. Consistently, in the heart of diabetic rats, the content of cytochrome b mRNA encoded by mitochondrial DNA was reduced to 50% of control (P < 0.01. This abnormal transcriptional activity of mitochondrial DNA could not be explained by mRNA or protein contents of mitochondrial transcription factor (mtTFA), but mtTFA binding to the promoter sequence of mitochondrial DNA, assessed by gel‐shift assay, was attenuated in diabetic rats. In contrast, the mRNA expression of nuclear‐encoded mitochondrial genes, such as ATP synthase‐β, was not affected by diabetes. Although O2 consumption of the mitochondria from diabetic rats was decreased, H2O2 production in these rats was increased compared with the control. Insulin treatment reversed all the abnormalities found in diabetic rats. These results clearly indicate that an impairment of binding activity of mtTFA to the promoter sequence has a key role in the abnormal mitochondrial gene expression, which might explain the mitochondrial dysfunction found in diabetic heart.
This paper references
In organello RNA synthesis system from mammalian liver and brain.
J. Enríquez (1996)
Identification and characterization of a gene regulating enzymatic glycosylation which is induced by diabetes and hyperglycemia specifically in rat cardiac tissue.
Y. Nishio (1995)
Deficiency of Cardiac β-Adrenergic Receptor in Streptozocin-Induced Diabetic Rats
Y. Nishio (1988)
An organellar RNA synthesis system from mammalian liver and brain
Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression
J. Wang (1999)
FIGURE 4. Interaction between mitochondrial dysfunction and oxidative stress in mitochondria
Altered Activities of Transcription Factors and Their Related Gene Expression in Cardiac Tissues of Diabetic Rats
Y. Nishio (1998)
Reduced activity of mtTFA decreases the transcription in mitochondria isolated from diabetic rat heart.
A. Kanazawa (2002)
Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells.
S. Ballinger (2000)
Amelioration of high fructose-induced matabolic derangements by activation of PPARα
永井 義夫 (2002)
Inhibition of mitochondrial gene expression by antisense RNA of mitochondrial transcription factor A (mtTFA)
H. Inagaki (1998)
Mitochondrial disease in superoxide dismutase 2 mutant mice.
S. Melov (1999)
Mitochondrial deoxyribonucleic acid content is specifically decreased in adult, but not fetal, pancreatic islets of the Goto-Kakizaki rat, a genetic model of noninsulin-dependent diabetes.
P. Serradas (1995)
Isolation of mitochondria with emphasis on heart mitochondria from small amounts of tissue.
L. Mela (1979)
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
T. Nishikawa (2000)
Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1
Z. Wu (1999)
Isolation of Rat Mitochondrial Transcription Factor A (r-Tfam) cDNA
H. Inagaki (2000)
Amelioration of high fructose-induced metabolic derangements by activation of PPARalpha.
Yoshio Nagai (2002)
Glucose induced genes in bovine aortic smooth muscle cells identified by mRNA differential display
Y. Nishio (1994)
Similarity of human mitochondrial transcription factor 1 to high mobility group proteins.
M. Parisi (1991)
Mitochondrial diseases in man and mouse.
D. Wallace (1999)
A transcription factor required for promoter recognition by human mitochondrial RNA polymerase. Accurate initiation at the heavy- and light-strand promoters dissected and reconstituted in vitro.
R. P. Fisher (1985)

This paper is referenced by
Nebivolol Improves Diastolic Dysfunction and Myocardial Remodeling Through Reductions in Oxidative Stress in the Zucker Obese Rat
Xinli Zhou (2010)
A high fructose diet alters affective-like behavior and metrics of synaptic mitochondrial function differentially in male and female rats
Alix H. Kloster (2019)
The metabolic syndrome induces early changes in the swine renal medullary mitochondria
A. Eirin (2017)
Contribution à l'étude du rôle physiologique de l'apolipoprotéine O
A. Turkieh (2012)
Overexpression of TFAM Protects 3T3-L1 Adipocytes from NYGGF4 (PID1) Overexpression-Induced Insulin Resistance and Mitochondrial Dysfunction
C. Shi (2012)
A novel heteroplasmic mitochondrial DNA mutation, A8890G, in a patient with juvenile‑onset metabolic syndrome: a case report.
W. Ye (2013)
Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease
J. Ren (2010)
Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)
Xichun Yu (2007)
Genetic Modification of the Heart Mouse models of mitochondrial dysfunction and heart failure
Laurie K. Russell (2005)
Tissue-specific implications of mitochondrial alterations in aging.
D. Liu (2013)
Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches.
F. Sanchis-Gomar (2014)
Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension.
Shruti S. Sharma (2008)
Hyperglycemia-induced mitochondrial alterations in liver.
A. Dey (2010)
Oxidative stress: a key contributor to diabetic cardiomyopathy.
M. Khullar (2010)
Perspectives and Potential Applications of Mitochondria‐Targeted Antioxidants in Cardiometabolic Diseases and Type 2 Diabetes
M. Rocha (2014)
Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia.
J. Lumini-Oliveira (2011)
Oxidative stress: a key contributor to diabetic
P. Singal (2010)
Diabetic cardiomyopathy revisited.
S. Boudina (2007)
Polimorfismos no gene Tfam e características de carcaça em novilhas da raça Nelore
D. R. Ayres (2008)
Therapeutic Potential of Lipoamide and Enhanced MitochondrialBiogenesis for Treatment of Insulin Resistance
Weili Shen (2012)
Diabetes and Cardiac Mitochondria
José Marín-García (2013)
Oxidative Stress and Pulmonary Vascular Disorders
Christine D. Gross (2014)
Role of ROS and RNS Sources in Physiological and Pathological Conditions
S. Di Meo (2016)
Diabetische Herzinsuffizienz
Michael Resl (2009)
The Role of Mitochondria in the Metabolic Syndrome and Insulin Resistance
J. Marín-García (2013)
Cellular senescence links aging and diabetes in cardiovascular disease.
Hadis Shakeri (2018)
Mouse models of mitochondrial dysfunction and heart failure.
Laurie K. Russell (2005)
Role of mitochondrial dysfunction in insulin resistance.
J. Kim (2008)
Asymmetric dimethylarginine inhibits HSP90 activity in pulmonary arterial endothelial cells: role of mitochondrial dysfunction.
Neetu Sud (2008)
Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep.
W. Jørgensen (2009)
High Fructose Diet Induces Sex-specific Modifications in Synaptic Respiration and Affective-like Behaviors in Rats
Alix Kloster (2019)
Characterisation of metabolic and mitochondrial dysfunction in the isoproterenol model of heart failure: the role of metformin
V. Peterson (2014)
See more
Semantic Scholar Logo Some data provided by SemanticScholar