Genes and exercise intolerance: insights from McArdle disease
McArdle disease (glycogen storage disease type V) is caused by inherited deficiency of a key enzyme in muscle metabolism, the skeletal muscle-specific isoform of glycogen phosphorylase, "myophosphorylase," which is encoded by the PYGM gene. Here we review the main pathophysiological, genotypic, and phenotypic features of McArdle disease and their interactions. To date, moderate-intensity exercise (together with pre-exercise carbohydrate ingestion) is the only treatment option that has proven useful for these patients. Furthermore, regular physical activity attenuates the clinical severity of McArdle disease. This is quite ...
Source: Physiological Genomics - January 27, 2016 Category: Genetics & Stem Cells Authors: Nogales-Gadea, G., Godfrey, R., Santalla, A., Coll-Canti, J., Pintos-Morell, G., Pinos, T., Arenas, J., Martin, M. A., Lucia, A. Tags: Systems Biology of Exercise Source Type: research
Rodent models for resolving extremes of exercise and health
The extremes of exercise capacity and health are considered a complex interplay between genes and the environment. In general, the study of animal models has proven critical for deep mechanistic exploration that provides guidance for focused and hypothesis-driven discovery in humans. Hypotheses underlying molecular mechanisms of disease and gene/tissue function can be tested in rodents to generate sufficient evidence to resolve and progress our understanding of human biology. Here we provide examples of three alternative uses of rodent models that have been applied successfully to advance knowledge that bridges our underst...
Source: Physiological Genomics - January 27, 2016 Category: Genetics & Stem Cells Authors: Garton, F. C., North, K. N., Koch, L. G., Britton, S. L., Nogales-Gadea, G., Lucia, A. Tags: Systems Biology of Exercise Source Type: research
Thyroid hormone receptor-{alpha} deletion decreases heart function and exercise performance in apolipoprotein E-deficient mice
In conclusion, the deletion of TRα in ApoE–/– mice alters cardiac structure and contractility; both could contribute to blunted BP response to physical exercise and impaired exercise performance. (Source: Physiological Genomics)
Source: Physiological Genomics - January 27, 2016 Category: Genetics & Stem Cells Authors: Liu, K. L., Canaple, L., del Carmine, P., Gauthier, K., Beylot, M., Lo, M. Tags: Call for Papers: Systems Biology and Polygenic Traits Source Type: research
Pappa2 is linked to salt-sensitive hypertension in Dahl S rats
A 1.37 Mbp region of chromosome 13 previously identified by exclusion mapping was consistently associated with a reduction of salt-induced hypertension in the Dahl salt-sensitive (SS) rat. This region contained five genes that were introgressed from the salt-insensitive Brown Norway (BN) rat. The goal of the present study was to further narrow that region to identify the gene(s) most likely to protect from salt-induced hypertension. The studies yielded a subcongenic SS rat strain containing a 0.71 Mbp insert from BN (26-P strain) in which salt-induced hypertension was reduced by 24 mmHg. The region contained two protein-co...
Source: Physiological Genomics - January 1, 2016 Category: Genetics & Stem Cells Authors: Cowley, A. W., Yang, C., Kumar, V., Lazar, J., Jacob, H., Geurts, A. M., Liu, P., Dayton, A., Kurth, T., Liang, M. Tags: Genetic and Genomics Investigation of Structure and Function of the Kidney Source Type: research
Effects of combined progesterone and 17{beta}-estradiol treatment on the transcriptome of cultured human myometrial smooth muscle cells
A transcriptomic analysis of cultured human uterine smooth muscle cells (hUtSMCs) was performed to examine gene expression profiles in smooth muscle in an environment containing the two major steroid hormones that regulate the human myometrium in physiological states associated with estrous, pregnancy, labor, and pathophysiological states such as leiomyoma and endometrial cancer. hUtSMCs were treated with progesterone (P4) and 17β-estradiol (E2) individually and in combination, in the presence and absence of RU486 (mifepristone). Transcription of many genes was modulated in the presence of P4 or E2 alone, but almost s...
Source: Physiological Genomics - January 1, 2016 Category: Genetics & Stem Cells Authors: Chandran, S., Cairns, M. T., O'Brien, M., O'Connell, E., Mashayekhi, K., Smith, T. J. Tags: Regulation of Gene Expression Source Type: research
Telomere dynamics during aging in polygenic left ventricular hypertrophy
Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR) and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological sequence beginning with fewer cardiomyocytes (2 days), leading to left ventricular hypertrophy (LVH) (13 wk) and subsequently progression to heart failure (38 wk). We measured telomere length, tissue activity of telomerase, mRNA levels of telomerase reverse transcriptase (Tert) and tel...
Source: Physiological Genomics - January 1, 2016 Category: Genetics & Stem Cells Authors: Marques, F. Z., Booth, S. A., Prestes, P. R., Curl, C. L., Delbridge, L. M. D., Lewandowski, P., Harrap, S. B., Charchar, F. J. Tags: Genomic and ' Polyomic Studies of Cardiovascular and Inflammatory Diseases Source Type: research
Pharmacogenomics of estrogens on changes in carotid artery intima-medial thickness and coronary arterial calcification: Kronos Early Estrogen Prevention Study
Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women (n = 606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. The association of treatment outcomes with variation in the same 764 candidate genes was evaluated in the same KEEPS participants 4 yr after randomization to either oral conjugated equine estrogens (0.45 mg/day), transdermal 17β-estradiol (50 μg/day...
Source: Physiological Genomics - January 1, 2016 Category: Genetics & Stem Cells Authors: Miller, V. M., Jenkins, G. D., Biernacka, J. M., Heit, J. A., Huggins, G. S., Hodis, H. N., Budoff, M. J., Lobo, R. A., Taylor, H. S., Manson, J. E., Black, D. M., Naftolin, F., Harman, S. M., de Andrade, M. Tags: General Interest Source Type: research
Protein-leucine ingestion activates a regenerative inflammo-myogenic transcriptome in skeletal muscle following intense endurance exercise
Protein-leucine supplement ingestion following strenuous endurance exercise accentuates skeletal-muscle protein synthesis and adaptive molecular responses, but the underlying transcriptome is uncharacterized. In a randomized single-blind triple-crossover design, 12 trained men completed 100 min of high-intensity cycling then ingested 70/15/180/30 g protein-leucine-carbohydrate-fat (15LEU), 23/5/180/30 g (5LEU), or 0/0/274/30 g (CON) beverages during the first 90 min of a 240 min recovery period. Vastus lateralis muscle samples (30 and 240 min postexercise) underwent transcriptome analysis by microarray followed by bioinfor...
Source: Physiological Genomics - January 1, 2016 Category: Genetics & Stem Cells Authors: Rowlands, D. S., Nelson, A. R., Raymond, F., Metairon, S., Mansourian, R., Clarke, J., Stellingwerff, T., Phillips, S. M. Tags: Nutrient Gene Interaction Source Type: research
Genetic loci associated with nonobstructive coronary artery disease in Caucasian women
Nonobstructive coronary artery disease (CAD) in women is associated with adverse cardiovascular (CV) outcomes; however, information regarding genetic variants that predispose women to nonobstructive CAD is lacking. Women from the Women's Ischemia Syndrome Evaluation (WISE) Study and the St. James Women Take Heart (WTH) Study were genotyped with the Cardio-MetaboChip. WISE enrolled women with symptoms and signs of ischemia referred for coronary angiography; WTH enrolled asymptomatic, community-based women without heart disease. Analyses were conducted with a case (WISE) - control (WTH) design and multivariate logistic regre...
Source: Physiological Genomics - January 1, 2016 Category: Genetics & Stem Cells Authors: Weng, L., Taylor, K. D., Chen, Y.-D. I., Sopko, G., Kelsey, S. F., Bairey Merz, C. N., Pepine, C. J., Miller, V. M., Rotter, J. I., Gulati, M., Goodarzi, M. O., Cooper-DeHoff, R. M. Tags: Omics Technologies and Applications Source Type: research
Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons
Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n = 7,781, ages: 20–104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, ...
Source: Physiological Genomics - January 1, 2016 Category: Genetics & Stem Cells Authors: Pilling, L. C., Joehanes, R., Kacprowski, T., Peters, M., Jansen, R., Karasik, D., Kiel, D. P., Harries, L. W., Teumer, A., Powell, J., Levy, D., Lin, H., Lunetta, K., Munson, P., Bandinelli, S., Henley, W., Hernandez, D., Singleton, A., Tanaka, T., van G Tags: Omics Technologies and Applications Source Type: research
Intrauterine growth restriction perturbs nucleosome depletion at a growth hormone-responsive element in the mouse IGF-1 gene
Intrauterine growth restriction (IUGR) is a common human pregnancy complication. IUGR offspring carry significant postnatal risk for early-onset metabolic syndrome, which is associated with persistent reduction in IGF-1 protein expression. We have previously shown that preadolescent IUGR male mice have decreased hepatic IGF-1 mRNA and circulating IGF-1 protein at postnatal day 21, the age when growth hormone (GH) normally upregulates hepatic IGF-1 expression. Here we studied nucleosome occupancy and CpG methylation at a putative growth hormone-responsive element in intron 2 (in2GHRE) of the hepatic IGF-1 gene in normal, sh...
Source: Physiological Genomics - December 1, 2015 Category: Genetics & Stem Cells Authors: McKnight, R. A., Yost, C. C., Yu, X., Wiedmeier, J. E., Callaway, C. W., Brown, A. S., Lane, R. H., Fung, C. M. Tags: Physiological Genomics of Cell States and Their Regulation and Single Cell Genomics Source Type: research
Gestation under chronic constant light leads to extensive gene expression changes in the fetal rat liver
Recent reports account for altered metabolism in adult offspring from pregnancy subjected to abnormal photoperiod, suggesting fetal programming of liver physiology. To generate a pipeline of subsequent mechanistic experiments addressing strong candidate genes, here we investigated the effects of constant gestational light on the fetal liver transcriptome. At 10 days of gestation, dams were randomized in two groups (n = 7 each): constant light (LL) and normal photoperiod (12 h light/12 h dark; LD). At 18 days of gestation, RNA was isolated from the fetal liver and subjected to DNA microarray (Affymetrix platform for 28,000 ...
Source: Physiological Genomics - December 1, 2015 Category: Genetics & Stem Cells Authors: Spichiger, C., Torres-Farfan, C., Galdames, H. A., Mendez, N., Alonso-Vazquez, P., Richter, H. G. Tags: General Interest Source Type: research
Cardioprotective and nonprotective regimens of chronic hypoxia diversely affect the myocardial antioxidant systems
It has been documented that adaptation to hypoxia increases myocardial tolerance to ischemia-reperfusion (I/R) injury depending on the regimen of adaptation. Reactive oxygen species (ROS) formed during hypoxia play an important role in the induction of protective cardiac phenotype. On the other hand, the excess of ROS can contribute to tissue damage caused by I/R. Here we investigated the relationship between myocardial tolerance to I/R injury and transcription activity of major antioxidant genes, transcription factors, and oxidative stress in three different regimens of chronic hypoxia. Adult male Wistar rats were exposed...
Source: Physiological Genomics - December 1, 2015 Category: Genetics & Stem Cells Authors: Kasparova, D., Neckar, J., Dabrowska, L., Novotny, J., Mraz, J., Kolar, F., Zurmanova, J. Tags: Regulation of Gene Expression Source Type: research
Changes in the transcriptome of bovine ovarian cortex during follicle activation in vitro
The signals that regulate activation, a key transition in ovarian follicular development, are still not well understood, especially in nonrodent species. To gain insight into the regulation of this transition in cattle, we combined a microarray approach with an in vitro system in which ovarian cortical pieces cultured in control medium are enriched for primordial follicles, whereas pieces cultured with insulin are enriched for primary follicles. Total RNA was extracted from cultured cortical pieces, and then transcripts were identified and analyzed using the Affymetrix Bovine Genome GeneChip array. Around 65% of the transc...
Source: Physiological Genomics - December 1, 2015 Category: Genetics & Stem Cells Authors: Yang, M. Y., Fortune, J. E. Tags: Regulation of Gene Expression Source Type: research
Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia
This study reports the microarray analysis of gene expression in cardiac and skeletal muscle in the colon 26 (C26) carcinoma mouse model of cancer cachexia. A total of 268 genes were found to be differentially expressed in cardiac muscle tissue, compared with nontumor-bearing controls. This was fewer than the 1,533 genes that changed in cachectic skeletal muscle. In addition to different numbers of genes changing, different cellular functions were seen to change in each tissue. The cachectic heart showed signs of inflammation, similar to cachectic skeletal muscle, but did not show the upregulation of ubiquitin-dependent pr...
Source: Physiological Genomics - December 1, 2015 Category: Genetics & Stem Cells Authors: Shum, A. M. Y., Fung, D. C. Y., Corley, S. M., McGill, M. C., Bentley, N. L., Tan, T. C., Wilkins, M. R., Polly, P. Tags: Regulation of Gene Expression Source Type: research
