Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function.
View Article and Find Full Text PDFPurpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 () are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between and pulmonary function.
View Article and Find Full Text PDFThe post-ionization dynamics of chemo-treated and untreated 4T1 breast cancer cells ionized by laser trapping techniques are studied. We have determined each cell's charge and refractive index by developing a theoretical model for the forces determining the post-ionization dynamics. The shift in a cell's refractive index due to an intense oscillating electric field was studied, and the results are reported here.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
March 2021
Human genome-wide association studies (GWASs) have identified more than 270 loci associated with pulmonary function; however, follow-up studies to determine causal genes at these loci are few. SNPs in low-density lipoprotein receptor-related protein 1 (LRP1) are associated with human pulmonary function in GWASs. Using murine models, we investigated the effect of genetic disruption of the gene in smooth muscle cells on pulmonary function in naive animals and after exposure to bacterial LPS or house dust mite extract.
View Article and Find Full Text PDFEnviron Epidemiol
August 2019
Background: Numerous health effects of smoking are well-known; associations with semen quality are uncertain. Most previous studies did not adjust for potential confounders and had limited information on age at smoking initiation or smoking cessation.
Methods: We investigated 1,631 healthy fertile men in the Nanjing Medical University Longitudinal Investigation of Fertility and the Environment (NMU-LIFE) study.
Background: Ambient air pollution is associated with numerous adverse health outcomes, but the underlying mechanisms are not well understood; epigenetic effects including altered DNA methylation could play a role. To evaluate associations of long-term air pollution exposure with DNA methylation in blood, we conducted an epigenome-wide association study in a Korean chronic obstructive pulmonary disease cohort (N = 100 including 60 cases) using Illumina's Infinium HumanMethylation450K Beadchip. Annual average concentrations of particulate matter ≤ 10 μm in diameter (PM) and nitrogen dioxide (NO) were estimated at participants' residential addresses using exposure prediction models.
View Article and Find Full Text PDFNano-titanium dioxide (nano-TiO), though one of the most utilized and produced engineered nanomaterials (ENMs), diminishes cardiovascular function through dysregulation of metabolism and mitochondrial bioenergetics following inhalation exposure. The molecular mechanisms governing this cardiac dysfunction remain largely unknown. The purpose of this study was to elucidate molecular mediators that connect nano-TiO exposure with impaired cardiac function.
View Article and Find Full Text PDF>99% of the mitochondrial proteome is nuclear-encoded. The mitochondrion relies on a coordinated multi-complex process for nuclear genome-encoded mitochondrial protein import. Mitochondrial heat shock protein 70 (mtHsp70) is a key component of this process and a central constituent of the protein import motor.
View Article and Find Full Text PDFNanotechnology offers innovation in products from cosmetics to drug delivery, leading to increased engineered nanomaterial (ENM) exposure. Unfortunately, health impacts of ENM are not fully realized. Titanium dioxide (TiO) is among the most widely produced ENM due to its use in numerous applications.
View Article and Find Full Text PDFCardiovascular disease is the primary cause of mortality for individuals with type 2 diabetes mellitus. During the diabetic condition, cardiovascular dysfunction can be partially attributed to molecular changes in the tissue, including alterations in microRNA (miRNA) interactions. MiRNAs have been reported in the mitochondrion and their presence may influence cellular bioenergetics, creating decrements in functional capacity.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
April 2017
Human genome-wide association studies have identified over 50 loci associated with pulmonary function and related phenotypes, yet follow-up studies to determine causal genes or variants are rare. Single nucleotide polymorphisms in serotonin receptor 4 () are associated with human pulmonary function in genome-wide association studies and follow-up animal work has demonstrated that is causally associated with pulmonary function in mice, although the precise mechanisms were not identified. We sought to elucidate the role of neural innervation and pulmonary architecture in the lung phenotype of animals.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
March 2017
Nanomaterial production is expanding as new industrial and consumer applications are introduced. Nevertheless, the impacts of exposure to these compounds are not fully realized. The present study was designed to determine whether gestational nano-sized titanium dioxide exposure impacts cardiac and metabolic function of developing progeny.
View Article and Find Full Text PDFEnhanced sensitivity in echocardiographic analyses may allow for early detection of changes in cardiac function beyond the detection limits of conventional echocardiographic analyses, particularly in a small animal model. The goal of this study was to compare conventional echocardiographic measurements and speckle-tracking based strain imaging analyses in a small animal model of type 1 diabetes mellitus. Conventional analyses revealed differences in ejection fraction, fractional shortening, cardiac output, and stroke volume in diabetic animals relative to controls at 6-weeks post-diabetic onset.
View Article and Find Full Text PDFThroughout the United States, air pollution correlates with adverse health outcomes, and cardiovascular disease incidence is commonly increased following environmental exposure. In areas surrounding active mountaintop removal mines (MTM), a further increase in cardiovascular morbidity is observed and may be attributed in part to particulate matter (PM) released from the mine. The mitochondrion has been shown to be central in the etiology of many cardiovascular diseases, yet its roles in PM-related cardiovascular effects are not realized.
View Article and Find Full Text PDFInterleukin-15 receptor alpha knockout (IL15RαKO) mice exhibit a greater skeletal muscle mitochondrial density with an altered mitochondrial morphology. However, the mechanism and functional impact of these changes have not been determined. In this study, we characterized the functional, proteomic, and genomic alterations in mitochondrial subpopulations isolated from the skeletal muscles of IL15RαKO mice and B6129 background control mice.
View Article and Find Full Text PDFBackground: Cardiomyocytes are rich in mitochondria which are situated in spatially distinct subcellular regions, including those under the plasma membrane, subsarcolemmal mitochondria, and those between the myofibrils, interfibrillar mitochondria. We previously observed subpopulation-specific differences in mitochondrial proteomes following diabetic insult. The objective of this study was to determine whether mitochondrial genome-encoded proteins are regulated by microRNAs inside the mitochondrion and whether subcellular spatial location or diabetes mellitus influences the dynamics.
View Article and Find Full Text PDFDue to the ongoing evolution of nanotechnology, there is a growing need to assess the toxicological outcomes in under-studied populations in order to properly consider the potential of engineered nanomaterials (ENM) and fully enhance their safety. Recently, we and others have explored the vascular consequences associated with gestational nanomaterial exposure, reporting microvascular dysfunction within the uterine circulation of pregnant dams and the tail artery of fetal pups. It has been proposed (via work derived by the Barker Hypothesis) that mitochondrial dysfunction and subsequent oxidative stress mechanisms as a possible link between a hostile gestational environment and adult disease.
View Article and Find Full Text PDFMitofilin, also known as heart muscle protein, is an inner mitochondrial membrane structural protein that plays a central role in maintaining cristae morphology and structure. It is a critical component of the mitochondrial contact site and cristae organizing system (MICOS) complex which is important for mitochondrial architecture and cristae morphology. Our laboratory has previously reported alterations in mitochondrial morphology and proteomic make-up during type 1 diabetes mellitus, with mitofilin being significantly down-regulated in interfibrillar mitochondria (IFM).
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
July 2014
The mitochondrion has been implicated in the development of diabetic cardiomyopathy. Examination of cardiac mitochondria is complicated by the existence of spatially distinct subpopulations including subsarcolemmal (SSM) and interfibrillar (IFM). Dysfunction to cardiac SSM has been reported in murine models of type 2 diabetes mellitus; however, subpopulation-based mitochondrial analyses have not been explored in type 2 diabetic human heart.
View Article and Find Full Text PDFAims: We have previously reported alterations in cardiolipin content and inner mitochondrial membrane (IMM) proteomic make-up specifically in interfibrillar mitochondria (IFM) in the type 1 diabetic heart; however, the mechanism underlying this alteration is unknown. The goal of this study was to determine how the cardiolipin biosynthetic pathway and cardiolipin-IMM protein interactions are impacted by type 1 diabetes mellitus.
Main Methods: Male FVB mice were made diabetic by multiple low-dose streptozotocin injections and sacrificed five weeks post-diabetic onset.
Compelling clinical reports reveal that behavioral stress alone is sufficient to cause reversible myocardial dysfunction in selected individuals. We developed a rodent stress cardiomyopathy model by a combination of prenatal and postnatal behavioral stresses (Stress). We previously reported a decrease in percent fractional shortening by echo, both systolic and diastolic dysfunction by catheter-based hemodynamics, as well as attenuated hemodynamic and inotropic responses to the β-adrenergic agonist, isoproterenol (ISO) in Stress rats compared with matched controls (Kan H, Birkle D, Jain AC, Failinger C, Xie S, Finkel MS.
View Article and Find Full Text PDFMitochondrial dysfunction is a contributor to diabetic cardiomyopathy. Previously, we observed proteomic decrements within the inner mitochondrial membrane (IMM) and matrix of diabetic cardiac interfibrillar mitochondria (IFM) correlating with dysfunctional mitochondrial protein import. The goal of this study was to determine whether overexpression of mitochondria phospholipid hydroperoxide glutathione peroxidase 4 (mPHGPx), an antioxidant enzyme capable of scavenging membrane-associated lipid peroxides in the IMM, could reverse proteomic alterations, dysfunctional protein import, and ultimately, mitochondrial dysfunction associated with the diabetic heart.
View Article and Find Full Text PDFObjective: Autoantibodies to aminoacyl transfer RNA synthetases, such as histidyl (Jo-1), threonyl (PL-7), alanyl (PL-12), glycyl (EJ), and isoleucyl (OJ), are closely associated with a subset of patients with polymyositis/dermatomyositis (PM/DM) complicated by interstitial lung disease (ILD). Anti-Jo-1 is by far the most common, found in 15-25% of patients with PM/DM, whereas the other types are found in only approximately 3% of these patients. In this study, the clinical associations of these autoantibodies in Japanese patients with PM/DM were investigated.
View Article and Find Full Text PDFScreening for disease-specific autoantibodies may be useful in asymptomatic ANA-positive individuals as a means of evaluating the risk of developing a systemic autoimmune disease such as systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), scleroderma (SSc), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or primary biliary cirrhosis (PBC) in the future. In patients with known or suspected systemic autoimmune disease, a panel of disease-specific markers may help to establish a diagnosis and to assess the prognosis. The great strides in autoantibody testing over the last 20 years make it feasible to use specific autoantibody markers to improve diagnostic accuracy in systemic autoimmune disease.
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