Chronic exposure to ambient particulate matter alters cardiac gene expression patterns and markers of oxidative stress in rats

Although short-term disuse does not result in measurable muscle atrophy, studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men ( n = 7, mean age ± SD = 22.1 ± 3.7 yr) following 48 h unloading (UL) via unilateral lower limb suspension and 24 h reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected at baseline, 48 h UL, and 24 h RL. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated with quantitative RT-PCR (qRT-PCR), and protein levels were measured with Western blot. Of the upregulated genes after UL, the most enriched functional group and highest ranked canonical pathway were related to protein ubiquitination. The oxidative stress response pathway was the second highest ranked canonical pathway. Of the downregulated genes, functions related to mitochondrial metabolism were the most highly enriched. In general, gene expression patterns following UL persisted following RL. qRT-PCR confirmed increases in mRNA for ubiquitin proteasome pathway-related E3 ligase Atrogin1 (but not accompanying increases in protein products) and stress response gene heme oxygenase-1 (HMOX, which showed a trend toward increases in protein products at 48 h UL) as well as extracellular matrix (ECM) component COL4A3. The gene expression patterns were not reversed on RL, suggesting that molecular responses to short-term periods of skeletal muscle inactivity may persist after activity resumes.

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A role for T lymphocytes in mediating cardiac diastolic function

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00073.2005 ◽

2005 ◽

Vol 289 (2) ◽

pp. H643-H651 ◽

Cited By ~ 50

Author(s):

Qianli Yu ◽

Ronald R. Watson ◽

John J. Marchalonis ◽

Douglas F. Larson

Keyword(s):

Gene Expression ◽

Diastolic Function ◽

Immune Modulation ◽

Expression Patterns ◽

Relative Proportion ◽

Wall Stress ◽

Left Ventricular ◽

Lymphocyte Function ◽

Cardiac Gene Expression ◽

Cardiac Gene

The induction of T helper (TH) lymphocytes by distinct TH ligands results in a differentiation to TH1/TH2 subsets based on their unique pattern of cytokine secretion and effector functions. We hypothesized that the relative proportion of TH1/TH2 directly relates to cardiac fibroblast (CF) function and thereby cardiac extracellular matrix (ECM) composition and cardiac diastolic function in the absence of injury or altered wall stress. We compared the effect of selective TH1 with TH2 inducers on cardiac gene expression, ECM composition, and diastolic function in C57BL/J mice. Twelve weeks after immune modulation, the left ventricular stiffness (β) was significantly increased in the TH1 group and decreased in the TH2 group ( P < 0.01). The TH2 group also demonstrated significantly increased end-diastolic and end-systolic volumes ( P < 0.01). Cardiac gene expression patterns for pro-matrix metalloproteinase (MMP)-9 and -13 were increased by greater than fivefold in the TH2 group and significantly decreased in the TH1 group ( P < 0.05). The total cardiac collagen and cross-linked collagen were significantly increased in the TH1 group and decreased in the TH2 group ( P < 0.01). Coculturing lymphocytes harvested from the treated mice with naive primary CF demonstrated a direct control of the lymphocytes on CF pro-collagen, pro-MMP gene expression, and MMP activity. These results suggest that the TH phenotype differentially affects diastolic function through modulating CF pro-collagen and pro-MMP gene expression, MMP activity, and cardiac collagen cross-linking, resulting in altered ECM composition. Thus modulation of TH lymphocyte function could promote adaptive remodeling in heart failure and postmyocardial infarction.

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Similar gene expression patterns characterize aging and oxidative stress in Drosophila melanogaster

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0307605101 ◽

2004 ◽

Vol 101 (20) ◽

pp. 7663-7668 ◽

Cited By ~ 263

Author(s):

G. N. Landis ◽

D. Abdueva ◽

D. Skvortsov ◽

J. Yang ◽

B. E. Rabin ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Drosophila Melanogaster ◽

Expression Patterns ◽

Gene Expression Patterns ◽

And Oxidative Stress ◽

Similar Gene

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Cigarette smoke-induced oxidative stress alters DNA methylation patterns in sperm and neurological gene expression patterns in offspring

Fertility and Sterility ◽

10.1016/j.fertnstert.2019.07.973 ◽

2019 ◽

Vol 112 (3) ◽

pp. e337

Author(s):

Patrick J. Murphy ◽

Jingtao Guo ◽

Timothy G. Jenkins ◽

John R. Hoidal ◽

Thomas Huecksteadt ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Dna Methylation ◽

Cigarette Smoke ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Methylation Patterns

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AZT-induced mitochondrial toxicity: an epigenetic paradigm for dysregulation of gene expression through mitochondrial oxidative stress

Physiological Genomics ◽

10.1152/physiolgenomics.00045.2015 ◽

2015 ◽

Vol 47 (10) ◽

pp. 447-454 ◽

Cited By ~ 9

Author(s):

Christopher A. Koczor ◽

Zhe Jiao ◽

Earl Fields ◽

Rodney Russ ◽

Tomika Ludaway ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Steady State ◽

Methylenetetrahydrofolate Reductase ◽

Antiviral Agents ◽

Gene Encoding ◽

Mitochondrial Oxidative Stress ◽

Cardiac Gene Expression ◽

Cardiac Gene ◽

Encoding Protein

Mitochondrial dysfunction causes oxidative stress and cardiomyopathy. Oxidative stress also is a side effect of dideoxynucleoside antiretrovirals (NRTI) and is observed in NRTI-induced cardiomyopathy. We show here that treatment with the NRTI AZT {1-[(2 R,4 S,5 S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione} modulates cardiac gene expression epigenetically through production of mitochondrially derived reactive oxygen species. Transgenic mice with ubiquitous expression of mitochondrially targeted catalase (MCAT) and C57Bl/6 wild-type mice littermates (WT) were administered AZT (0.22 mg/day po, 35 days), and cardiac DNA and mRNA were isolated. In AZT-treated WT, 95 cardiac genes were differentially expressed compared with vehicle-treated WTs. When MCAT mice were treated with AZT, each of those 95 genes reverted toward the expression of vehicle-treated WTs. In AZT-treated WT hearts, Mthfr [5,10-methylenetetrahydrofolate reductase; a critical enzyme in synthesis of methionine cycle intermediates including S-adenosylmethionine (SAM)], was overexpressed. Steady-state abundance of SAM in cardiac extracts from AZT-treated MCAT mice increased 60% above that of vehicle-treated MCAT. No such change occurred in WT. AZT caused hypermethylation (47%) and hypomethylation (53%) of differentially methylated DNA regions in WT cardiac DNA. AZT-treated MCAT heart DNA exhibited greater hypermethylation (91%) and less hypomethylation (9%) compared with vehicle-treated MCAT controls. The gene encoding protein kinase C-α displayed multifocal epigenetic regulation caused by oxidative stress. Results show that mitochondrially derived oxidative stress in the heart hinders cardiac DNA methylation, alters steady-state abundance of SAM, alters cardiac gene expression, and promotes characteristic pathophysiological changes of cardiomyopathy. This mechanism for NRTI toxicity offers insight into long-term side effects from these commonly used antiviral agents.

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