AJP: Lung Cellular and Molecular Physiology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

The unfolded protein response controls ER stress-induced apoptosis of lung epithelial cells through angiotensin generation
This study tested the hypothesis that ER stress-induced apoptosis of human AECs might be mediated by influence of the unfolded protein response (UPR) on the autocrine ANGII/ANG1-7 system. A549 cells were challenged with MG132 or SP-C BRICHOS domain mutant G100S to induce ER stress and activation of UPR pathways. The results showed that either MG132 or G100S SP-C mutation activated all three canonical pathways of the UPR (IRE1/XBP1, ATF6, and PERK/eIF2α), which led to a significant increase in cathepsin D or in TACE (an ACE-2 ectodomain shedding enzyme) and eventually caused AEC apoptosis. However, ER stress-induced A...
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: Nguyen, H., Uhal, B. D. Tags: CALL FOR PAPERS Source Type: research

Regulation of pulmonary endothelial barrier function by kinases
The pulmonary endothelium is the target of continuous physiological and pathological stimuli that affect its crucial barrier function. The regulation, defense, and repair of endothelial barrier function require complex biochemical processes. This review examines the role of endothelial phosphorylating enzymes, kinases, a class with profound, interdigitating influences on endothelial permeability and lung function. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: Barabutis, N., Verin, A., Catravas, J. D. Tags: REVIEWS Source Type: research

Update on novel targets and potential treatment avenues in pulmonary hypertension
Pulmonary hypertension (PH) is a condition marked by a combination of constriction and remodeling within the pulmonary vasculature. It remains a disease without a cure, as current treatments were developed with a focus on vasodilatory properties but do not reverse the remodeling component. Numerous recent advances have been made in the understanding of cellular processes that drive pathologic remodeling in each layer of the vessel wall as well as the accompanying maladaptive changes in the right ventricle. In particular, the past few years have yielded much improved insight into the pathways that contribute to altered meta...
Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: Huetsch, J. C., Suresh, K., Bernier, M., Shimoda, L. A. Tags: PERSPECTIVES Source Type: research

Role of IQGAP1 in endothelial barrier enhancement caused by OxPAPC
This study evaluated the role for the multifunctional Rac1/Cdc42 effector and regulator, IQ domain containing GTPase-activating protein (IQGAP1), as a molecular transducer of the OxPAPC-mediated EC barrier-enhancing signal. IQGAP1 knockdown in endothelial cells by gene-specific small-interfering RNA abolished OxPAPC-induced enlargement of VE-cadherin-positive adherens junctions, suppressed peripheral accumulation of actin polymerization regulators, namely cortactin, neural Wiskott-Aldrich syndrome protein (N-WASP), and actin-related protein 3, and attenuated remodeling of the peripheral actin cytoskeleton. Inhibition of Ox...
Source: AJP: Lung Cellular and Molecular Physiology - October 9, 2016 Category: Respiratory Medicine Authors: Tian, Y., Tian, X., Gawlak, G., Sarich, N., Sacks, D. B., Birukova, A. A., Birukov, K. G. Tags: ARTICLES Source Type: research

2-Aminoethyldiphenylborinate modifies the pulmonary circulation in pulmonary hypertensive newborn lambs partially gestated at high altitude
Calcium signaling through store-operated channels (SOC) is involved in hypoxic pulmonary hypertension. We determined whether a treatment with 2-aminoethyldiphenylborinate (2-APB), a compound with SOC blocker activity, reduces pulmonary hypertension and vascular remodeling. Twelve newborn lambs exposed to perinatal chronic hypoxia were studied, six of them received a 2-APB treatment and the other six received vehicle treatment for 10 days in both cases. Throughout this period, we recorded cardiopulmonary variables and on day 11 we evaluated the response to an acute hypoxic challenge. Additionally, we assessed the vasoconstr...
Source: AJP: Lung Cellular and Molecular Physiology - October 9, 2016 Category: Respiratory Medicine Authors: Castillo-Galan, S., Quezada, S., Moraga, F., Ebensperger, G., Herrera, E. A., Benaldo, F., Hernandez, I., Ebensperger, R., Ramirez, S., Llanos, A. J., Reyes, R. V. Tags: CALL FOR PAPERS Source Type: research

Pathophysiologic evaluation of the transgenic CFTR "gut-corrected" porcine model of cystic fibrosis
This study evaluated the pulmonary pathophysiology of pigs with transgenic CFTR "gut-corrected" cystic fibrosis (CF). Four sows produced 18 piglets of which 11 were stillborn, with only 2 animals surviving beyond 2 wk. Failure to survive beyond the neonatal period by five piglets was judged to result from metabolic dysfunction related to genetic manipulation for CFTR gut expression or due to cloning artifact. Plasma analysis showed very low plasma proteins, highly elevated liver enzymes, and severe acidosis. All surviving offspring received furosemide for systemic edema. Physiologic evaluation was performed with lung tissu...
Source: AJP: Lung Cellular and Molecular Physiology - October 9, 2016 Category: Respiratory Medicine Authors: Ballard, S. T., Evans, J. W., Drag, H. S., Schuler, M. Tags: ARTICLES Source Type: research

Effects of suplatast tosilate on acutely dissociated sensory and paratracheal ganglia neurons
In this study, we investigated the effects of suplatast on acutely dissociated single neurons of sensory and paratracheal ganglia using a patch-clamp technique. Suplatast had little effect on various responses caused by capsaicin, acid, bradykinin, serotonin, and adenosine 5'-triphosphate in rat sensory neurons. Suplatast, even at 10–3 M, also did not induce any current at various membrane potentials in rat and guinea pig paratracheal ganglia neurons. Furthermore, acetylcholine- and bradykinin-induced depolarizations were not affected by suplatast. On the other hand, in rat paratracheal ganglia neurons, 10–5 M ...
Source: AJP: Lung Cellular and Molecular Physiology - October 9, 2016 Category: Respiratory Medicine Authors: Zhou, J.-R., Shirasaki, T., Soeda, F., Takahama, K. Tags: ARTICLES Source Type: research

How does pulmonary endarterectomy cure CTEPH: a clue to cure PAH?
Chronic thromboembolic pulmonary hypertension (CTEPH) is a hot topic in the field of pulmonary hypertension because many CTEPH patients are now curable by surgical pulmonary endarterectomy. However, there are still uncertainties regarding the pathogenesis of CTEPH, specifically how and where the small vessel arteriopathy that is indistinguishable from that in pulmonary arterial hypertension (plexogenic arteriopathy) develops and how pulmonary endarterectomy improves hemodynamics and possibly cures CTEPH. Based on our recent experimental finding that hemodynamic stress is fundamental for the development of plexogenic arteri...
Source: AJP: Lung Cellular and Molecular Physiology - October 9, 2016 Category: Respiratory Medicine Authors: Oka, M., McMurtry, I. F., Oshima, K. Tags: PERSPECTIVES Source Type: research

Cadmium attenuates the macrophage response to LPS through inhibition of the NF-{kappa}B pathway
Chronic obstructive pulmonary disease (COPD) in the U.S. is primarily caused by cigarette smoking. COPD patients are highly susceptible to respiratory infections in part due to alveolar macrophage dysfunction despite a substantial increase in macrophages in the lung. Cadmium (Cd) is a toxic metal that is concentrated within tobacco and accumulates in the lung of smokers. We hypothesized that Cd uptake into macrophages alters immune function thereby impairing the macrophage response to invading pathogens. Our hypothesis was tested by comparing primary human monocytes and macrophages, primary mouse bronchoalveolar lavage mye...
Source: AJP: Lung Cellular and Molecular Physiology - September 30, 2016 Category: Respiratory Medicine Authors: Cox, J. N., Rahman, M. A., Bao, S., Liu, M., Wheeler, S. E., Knoell, D. L. Tags: ARTICLES Source Type: research

Tetrahydrobiopterin oral therapy recouples eNOS and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs
We previously showed that newborn piglets who develop pulmonary hypertension during exposure to chronic hypoxia have diminished pulmonary vascular nitric oxide (NO) production and evidence of endothelial NO synthase (eNOS) uncoupling (Fike CD, Dikalova A, Kaplowitz MR, Cunningham G, Summar M, Aschner JL. Am J Respir Cell Mol Biol 53: 255–264, 2015). Tetrahydrobiopterin (BH4) is a cofactor that promotes eNOS coupling. Current clinical strategies typically invoke initiating treatment after the diagnosis of pulmonary hypertension, rather than prophylactically. The major purpose of this study was to determine whether sta...
Source: AJP: Lung Cellular and Molecular Physiology - September 30, 2016 Category: Respiratory Medicine Authors: Dikalova, A., Aschner, J. L., Kaplowitz, M. R., Summar, M., Fike, C. D. Tags: ARTICLES Source Type: research

Clinically relevant timing of antenatal sildenafil treatment reduces pulmonary vascular remodeling in congenital diaphragmatic hernia
We examined the effects of prenatal treatment with the phosphodiesterase-5 inhibitor sildenafil on pulmonary vascular development in experimental CDH starting at a clinically relevant time. The well-established, nitrofen-induced CDH rodent model was treated daily with 100 mg/kg sildenafil from day 17.5 until day 20.5 of gestation (E17.5–20.5). Importantly, this timing perfectly corresponds to the developmental stage of the lung at 20 wk of human gestation, when CDH is detectable by 2D-ultrasonography and/or MRI. At E21.5 pups were delivered by caesarean section and euthanized by lethal injection of pentobarbital. The...
Source: AJP: Lung Cellular and Molecular Physiology - September 30, 2016 Category: Respiratory Medicine Authors: Mous, D. S., Kool, H. M., Buscop-van Kempen, M. J., Koning, A. H., Dzyubachyk, O., Wijnen, R. M. H., Tibboel, D., Rottier, R. J. Tags: CALL FOR PAPERS Source Type: research

Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications
Posttranslational modifications add diversity to protein function. Throughout its life cycle, the cystic fibrosis transmembrane conductance regulator (CFTR) undergoes numerous covalent posttranslational modifications (PTMs), including glycosylation, ubiquitination, sumoylation, phosphorylation, and palmitoylation. These modifications regulate key steps during protein biogenesis, such as protein folding, trafficking, stability, function, and association with protein partners and therefore may serve as targets for therapeutic manipulation. More generally, an improved understanding of molecular mechanisms that underlie CFTR P...
Source: AJP: Lung Cellular and Molecular Physiology - September 30, 2016 Category: Respiratory Medicine Authors: McClure, M. L., Barnes, S., Brodsky, J. L., Sorscher, E. J. Tags: CALL FOR PAPERS Source Type: research

There is blood in the water: hemolysis, hemoglobin, and heme in acute lung injury
The major role of red blood cells (RBCs) is to deliver oxygen and remove carbon dioxide within organisms through the unique properties of hemoglobin. Although beneficial within RBCs, when outside hemoglobin and its breakdown products (heme, iron) induce proinflammatory responses affecting various cellular responses. Although these effects are considered to be prominent in disorders with increased hemolysis, recent evidence suggests that this process may be active in nonhemolytic disorders such as acute lung injury/acute respiratory distress syndrome. This perspectives article focuses on data related to red cell products in...
Source: AJP: Lung Cellular and Molecular Physiology - September 30, 2016 Category: Respiratory Medicine Authors: Gaggar, A., Patel, R. P. Tags: PERSPECTIVES Source Type: research

Interstitial pneumonia induced by bleomycin treatment is exacerbated in Angptl2-deficient mice
Angiopoietin-like protein 2 (ANGPTL2) is a chronic inflammatory mediator that, when deregulated, is associated with various pathologies. However, little is known about its activity in lung. To assess a possible lung function, we generated a rabbit monoclonal antibody that specifically recognizes mouse ANGPTL2 and then evaluated protein expression in mouse lung tissue. We observed abundant ANGPTL2 expression in both alveolar epithelial type I and type II cells and in resident alveolar macrophages under normal conditions. To assess ANGPTL2 function, we compared lung phenotypes in Angptl2 knockout (KO) and wild-type mice but ...
Source: AJP: Lung Cellular and Molecular Physiology - September 30, 2016 Category: Respiratory Medicine Authors: Motokawa, I., Endo, M., Terada, K., Horiguchi, H., Miyata, K., Kadomatsu, T., Morinaga, J., Sugizaki, T., Ito, T., Araki, K., Morioka, M. S., Manabe, I., Samukawa, T., Watanabe, M., Inoue, H., Oike, Y. Tags: ARTICLES Source Type: research

CCSP G38A polymorphism environment interactions regulate CCSP levels differentially in COPD
Impaired airway homeostasis in chronic obstructive pulmonary disease (COPD) could be partly related to club cell secretory protein (CCSP) deficiency. We hypothesize that CCSP G38A polymorphism is involved and aim to examine the influence of the CCSP G38A polymorphism on CCSP transcription levels and its regulatory mechanisms. CCSP genotype and CCSP levels in serum and sputum were assessed in 66 subjects with stable COPD included in a 1-yr observational study. Forty-nine of them had an exacerbation. In an in vitro study, the impact on the CCSP promoter of 38G wild-type or 38A variant was assessed. BEAS-2B cells were transfe...
Source: AJP: Lung Cellular and Molecular Physiology - September 30, 2016 Category: Respiratory Medicine Authors: Knabe, L., Varilh, J., Bergougnoux, A., Gamez, A.-S., Bonini, J., Pommier, A., Petit, A., Molinari, N., Vachier, I., Taulan-Cadars, M., Bourdin, A. Tags: ARTICLES Source Type: research