Effect of atorvastatin combined with coenzyme Q10 on uncoupling protein 2 gene expression in rats with heart failure after myocardial infarction

We searched for the presence of uncoupling protein genes so far unknown in marsupials and monotremes and identified uncoupling protein 2 (UCP2) and UCP3 full-length cDNAs in libraries constructed from the marsupials Antechinus flavipes and Sminthopsis macroura. Marsupial UCP2 is 89–90% identical to rodent UCP2, whereas UCP3 exhibits 80% identity to mouse UCP3. A phylogenetic tree including all known UCPs positions the novel marsupial UCP2 and UCP3 at the base of the mammalian orthologs. In the 5′-untranslated region of UCP2 a second open reading frame encoding for a 36-amino acid peptide was identified which is highly conserved in all vertebrate UCP2 transcripts. Analysis of tissue specificity in A. flavipes with homologous cDNA probes revealed ubiquitous presence of UCP2 mRNA and striated muscle specificity of UCP3 mRNA resembling the known expression pattern in rodents. Neither UCP2 nor UCP3 gene expression was stimulated in adipose tissue and skeletal muscle of cold exposed A. flavipes. However, UCP3 mRNA expression was upregulated 6-fold in heart and 2.5-fold in skeletal muscle as reported for rodents in response to fasting. Furthermore, UCP3 mRNA seems to be coregulated with PDK4 mRNA, indicating a relation to enhanced lipid metabolism. In contrast, UCP2 gene expression was not regulated in response to fasting in adipose tissue and skeletal muscle but was diminished in the lung and increased in adipose tissue. Taken together, the sequence analysis, tissue specificity and physiological regulation suggest a conserved function of UCP2 and UCP3 during 130 million years of mammalian evolution.

Download Full-text

Tissue-specific gene expression and functional regulation of uncoupling protein 2 (UCP2) by hypoxia and nutrient availability in gilthead sea bream (Sparus aurata): implications on the physiological significance of UCP1–3 variants

Fish Physiology and Biochemistry ◽

10.1007/s10695-013-9882-7 ◽

2013 ◽

Vol 40 (3) ◽

pp. 751-762 ◽

Cited By ~ 22

Author(s):

Azucena Bermejo-Nogales ◽

Josep Alvar Calduch-Giner ◽

Jaume Pérez-Sánchez

Keyword(s):

Gene Expression ◽

Nutrient Availability ◽

Sparus Aurata ◽

Uncoupling Protein ◽

Physiological Significance ◽

Sea Bream ◽

Specific Gene ◽

Uncoupling Protein 2 ◽

Tissue Specific Gene ◽

Functional Regulation

Download Full-text

Transcriptional regulation of uncoupling protein-2 gene expression in L6 myotubes

International Journal of Obesity ◽

10.1038/sj.ijo.0801812 ◽

2001 ◽

Vol 25 (11) ◽

pp. 1619-1624 ◽

Cited By ~ 10

Author(s):

Y Hatakeyama ◽

PJ Scarpace

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

L6 Myotubes

Download Full-text

Low-Frequency Electro-Acupuncture and Physical Exercise Improve Metabolic Disturbances and Modulate Gene Expression in Adipose Tissue in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome

Endocrinology ◽

10.1210/en.2008-0053 ◽

2008 ◽

Vol 149 (7) ◽

pp. 3559-3568 ◽

Cited By ~ 70

Author(s):

Louise Mannerås ◽

Ingibjörg H. Jonsdottir ◽

Agneta Holmäng ◽

Malin Lönn ◽

Elisabet Stener-Victorin

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Polycystic Ovary ◽

Uncoupling Protein ◽

Low Frequency ◽

Uncoupling Protein 2 ◽

Metabolic Disturbances ◽

Ovary Syndrome ◽

Adipose Tissue Gene Expression

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. Pharmacotherapy is often unsatisfactory. This study evaluates the effects of low-frequency electro-acupuncture (EA) and physical exercise on metabolic disturbances and adipose tissue mRNA expression of selected genes in a rat PCOS model characterized by insulin resistance and adiposity. Dihydrotestosterone (inducing PCOS) or vehicle (control) was administrated continuously, beginning before puberty. At age 10 wk, PCOS rats were randomly divided into three groups; PCOS, PCOS EA, and PCOS exercise. PCOS EA rats received 2-Hz EA (evoking muscle twitches) three times/wk during 4–5 wk. PCOS exercise rats had free access to a running wheel for 4–5 wk. EA and exercise improved insulin sensitivity, measured by clamp, in PCOS rats. Exercise also reduced adiposity, visceral adipocyte size, and plasma leptin. EA increased plasma IGF-I. Real-time RT-PCR revealed increased expression of leptin and IL-6 and decreased expression of uncoupling protein 2 in visceral adipose tissue of PCOS rats compared with controls. EA restored the expression of leptin and uncoupling protein 2, whereas exercise normalized adipose tissue leptin and IL-6 expression in PCOS rats. Thus, EA and exercise ameliorate insulin resistance in rats with PCOS. This effect may involve regulation of adipose tissue metabolism and production because EA and exercise each partly restore divergent adipose tissue gene expression associated with insulin resistance, obesity, and inflammation. In contrast to exercise, EA improves insulin sensitivity and modulates adipose tissue gene expression without influencing adipose tissue mass and cellularity.

Download Full-text

Abstract 4328: Integrated Network and Microarray Analysis to Identify New Biomarkers of Heart Failure after Myocardial Infarction

Circulation ◽

10.1161/circ.118.suppl_18.s_864-d ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Yvan Devaux ◽

Céline Yvorra ◽

Mélanie Vausort ◽

Céline Jeanty ◽

Francisco Azuaje ◽

...

Keyword(s):

Gene Expression ◽

Myocardial Infarction ◽

Heart Failure ◽

Growth Factor ◽

Microarray Analysis ◽

Prediction Models ◽

Differentially Expressed ◽

Reference Database ◽

Ppi Network ◽

New Biomarkers

Purpose : A significant proportion of acute myocardial infarction (MI) patients develop heart failure (HF). Early identification of patients at risk of developing HF after MI would be a major breakthrough. An approach combining the power of biological information networks and the precision of microarray analysis was undertaken to identify new biomarkers of HF. Methods : Since angiogenesis may be related to MI and HF, a protein-protein interaction (PPI) network was constructed by first extracting from the Entrez-Gene database a set of genes relevant to angiogenesis and MI. These genes were used as inputs to retrieve annotated interactions from the Human Protein Reference Database. Potential biomarkers were identified by network analysis. Gene expression profiles of blood cells taken at the time of MI in two groups of 16 patients (high ejection fraction (EF) at 1 month, EF≥45% and low EF at 1 month, EF≤40%) were obtained using oligonucleotide microarrays containing 25,000 genes and compared by Statistical Analysis of Microarrays (SAM). Prediction models based on machine learning were used to classify low and high EF patients. Results : SAM identified 525 genes differentially expressed between patients with high and low EF (fold-change ≥1.3). The PPI network included 556 nodes (proteins) and 686 edges (interactions). A network clustering algorithm identified 53 proteins highly specialized in growth and regulation processes. Out of these, 38 were found differentially expressed by SAM. Further filtering reported 3 genes as the optimal biomarker set: Vascular Endothelial Growth Factor B (VEGFB), Placental Growth Factor (PGF), both pro-angiogenic, and the anti-angiogenic protein Thrombospondin-1 (THBS1). Prediction models reported areas under the receiver operating characteristic curve (AUC) of 0.82 for this biomarker set. Conclusion : The classification performances achieved with the 3 biomarkers stresses the prognostic value of genes involved in angiogenesis. The network-based approach allowed us to identify powerful biomarkers, which could not be identified by applying standard gene expression data analysis only. Therefore, combined network and microarray analysis allows a systematic and less biased approach to biomarker discovery.

Download Full-text