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American Journal of Physiology. Cell Physiology

Iwona Hirschler-Laszkiewicz, Shu-Jen Chen, Lei Bao, JuFang Wang, Xue-Qian Zhang, Santhanam Shanmughapriya, Kerry Keefer, Muniswamy Madesh, Joseph Y Cheung, Barbara A Miller
Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential function in cell survival and is highly expressed in many cancers. Inhibition of TRPM2 in neuroblastoma by depletion with CRISPR technology or expression of dominant negative TRPM2-S has been shown to significantly reduce cell viability. Here, the role of proline-rich tyrosine kinase 2 (Pyk2) in TRPM2 modulation of neuroblastoma viability was explored. In TRPM2-depleted cells, phosphorylation and expression of Pyk2 and CREB, a downstream target, were significantly reduced after application of the chemotherapeutic agent doxorubicin...
July 18, 2018: American Journal of Physiology. Cell Physiology
Jessica Vanderstraeten, Hanane Derradji, Pierre Sonveaux, Ides Colin, Marie-Christine Many, Anne-Catherine Gérard
Iodine deficiency (ID), which affects almost two billion people worldwide, is associated with breast pathologies such as fibrosis in human and induces breast atypia in animal models. Because ID induces vascular activation in the thyroid, another iodide-uptaking organ, and as breast is also sensitive to ID, we aimed to characterize ID-induced effects on the breast microvasculature in vivo and in two different breast cell lines in vitro. Virgin and lactating NMRI mice received an iodide-deficient diet and a Na+ /I- symporter inhibitor for one to 20 days...
July 18, 2018: American Journal of Physiology. Cell Physiology
Daniel Jung, Altayeb Alshaikh, Sireesha Ratakonda, Mohamed Bashir, Md Ruhul Amin, Sohee Jeon, Jan Stevens, Sapna Sharma, Wahaj Ahmed, Mark Musch, Hatim Hassan
Most kidney stones (KS) are composed of calcium oxalate, and small increases in urine oxalate affect the stone risk. Intestinal oxalate secretion mediated by anion exchanger SLC26A6 (PAT1) plays a crucial role in limiting net absorption of ingested oxalate; thereby preventing hyperoxaluria and related KS, reflecting the importance of understanding regulation of intestinal oxalate transport. We previously showed that ATP and UTP inhibit oxalate transport by human intestinal Caco2-BBE cells (C2). Since ATP is rapidly degraded to adenosine (ADO), we examined whether intestinal oxalate transport is regulated by ADO...
July 18, 2018: American Journal of Physiology. Cell Physiology
Lin Cai, Xiao Li, Chong Geng, Xuelian Lei, Chunhui Wang
Intestinal barrier dysfunction plays a crucial role in the pathogenesis of ulcerative colitis (UC). Previous studies have shown somatostatin (SST) can protect intestinal barrier structure possibly through up-regulating tight junction (TJ) protein expression, but the mechanisms of this up-regulation remain undefined. This study aimed to investigate the molecular mechanisms of interaction of SST with its downstream regulatory elements in DSS-induced colitis mice. In DSS-induced colitis mice, exogenous SST supplement (octreotide) effectively ameliorated disease progression, restored colonic barrier structure and function, and stimulated claudin-4 expression...
July 18, 2018: American Journal of Physiology. Cell Physiology
Kaela M Varberg, Rashell O Garretson, Emily K Blue, Chenghao Chu, Cassandra R Gohn, Wanzhu Tu, Laura S Haneline
Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including hypertension and cardiovascular disease. A key mechanism by which these complications occur is through the functional impairment of vascular progenitor cells, including endothelial colony forming cells (ECFCs). Previously, we showed that fetal ECFCs exposed to GDM have decreased vasculogenic potential and altered gene expression. In this study, we evaluate whether transgelin (TAGLN), which is increased in GDM-exposed ECFCs, contributes to vasculogenic dysfunction...
June 27, 2018: American Journal of Physiology. Cell Physiology
Elodie Saudrais, Nathalie Strazielle, Jean-Francois Ghersi-Egea
Hydrogen peroxide, released at low physiological concentration, is involved in different cell signaling pathways during brain development. When released at supraphysiological concentrations in brain fluids following an inflammatory, hypoxic or toxic stress, it can initiate lipid peroxidation, protein and nucleic acid damage and contribute to long-term neurological impairment associated with perinatal diseases. We found high glutathione peroxidase and glutathione reductase enzymatic activities in both lateral and fourth ventricle choroid plexus tissue isolated from developing rats, in comparison to the cerebral cortex and liver...
June 27, 2018: American Journal of Physiology. Cell Physiology
Wazir Abdullahi, Dinesh Tripathi, Patrick T Ronaldson
The blood-brain barrier (BBB) is a physical and biochemical barrier that precisely controls cerebral homeostasis. It also plays a central role in the regulation of blood-to-brain flux of endogenous and exogenous xenobiotics and associated metabolites. This is accomplished by molecular characteristics of brain microvessel endothelial cells such as tight junction protein complexes and functional expression of influx and efflux transporters. One of the pathophysiological features of ischemic stroke is disruption of the BBB, which significantly contributes to development of brain injury and subsequent neurological impairment...
June 27, 2018: American Journal of Physiology. Cell Physiology
Ashley N Oliveira, David A Hood
The mitochondrial unfolded protein response (UPRmt ) is a protein quality control mechanism that strives to achieve proteostasis in the face of misfolded proteins. Due to the reliance of mitochondria on both the nuclear and mitochondrial genomes, a perturbation of the coordination of these genomes results in a mito-nuclear imbalance in which holoenzymes are unable to assume mature stoichiometry and thereby activates the UPRmt . Thus, we sought to perturb this genomic coordination by using a systemic anti-sense oligonucleotide (in-vivo Morpholino) targeted to Tim23, the major channel of the inner membrane...
June 27, 2018: American Journal of Physiology. Cell Physiology
Wenli Liu, Yueqin Liu, Hongzhen Li, Griffin P Rodgers
Neutrophils increase production of reactive oxygen species, including superoxide, hydrogen peroxide (H2 O2 ), and hydroxyl radical, to destroy invading microorganisms under pathological conditions. Conversely, oxidative-stress conditions, such as the presence of H2 O2 , induce neutrophil apoptosis, which helps to remove neutrophils after inflammation. However, the detailed molecular mechanisms that are involved in the latter process have not been elucidated. In this study, we investigated the potential role of olfactomedin 4 (Olfm4) in oxidative stress (H2 O2 )-induced superoxide production and apoptosis in mouse neutrophils...
June 27, 2018: American Journal of Physiology. Cell Physiology
Fang Xin, Yuan Cheng, Jie Ren, Sitao Zhang, Ping Liu, Haiyan Zhao, Haixia Huang, Wei Wang
The large conductance Ca2+ -activated potassium (BKCa ) channel is activated by stretch. The stress regulated exon (STREX) in α subunits is known to affect mechanosensitivity of BKCa channels. However, in human colonic smooth muscle cells (HCoSMCs) we found that the α subunits without STREX (ZERO-BK) and β1 subunits could be detected yet the cells were mechanosensitive. Whether the β1 subunit is involved in the regulation of BKCa mechanosensitivity is unclear. In the present study, ZERO-BK and β1 subunits were individually expressed or coexpressed in HEK293 cells and cell-attached patch-clamp techniques were used to measure BKCa currents defining mechanosensitivity...
June 20, 2018: American Journal of Physiology. Cell Physiology
Marwa M Qadri, Gregory D Jay, Rennolds S Ostrom, Ling X Zhang, Khaled A Elsaid
Osteoarthritis (OA) is characterized by synovitis and synovial fibrosis. Synoviocytes are fibroblast-like resident cells of the synovium that are activated by TGF-β to proliferate, migrate and produce extracellular matrix. Synoviocytes secrete hyaluronan (HA) and proteoglycan-4 (PRG4). HA reduced synovial fibrosis in vivo and the Prg4-/- mouse exhibits synovial hyperplasia. We investigated the antifibrotic effects of increased intracellular cAMP in TGF-β stimulated human OA synoviocytes. TGF-β1 stimulated collagen I (COL1A1), α-SMA, TIMP-1, PLOD2 expression and procollagen I, α-SMA, HA and PRG4 production, migration and proliferation of OA synoviocytes were measured...
June 13, 2018: American Journal of Physiology. Cell Physiology
Shiyuan Huang, Xiaona Wang, Xinmei Wu, Jiale Yu, JinJing Li, Xiaoyuan Huang, Chunfang Zhu, Hongshan Ge
Yes-associated protein (Yap) was the core transcriptional co-activator in the downstream Hippo pathway that regulated cell proliferation and tissue growth. However, its role in the regulation of myoblast differentiation remains unclear. Regulation of mitochondrial networks by dynamin-related protein 1 (Drp1) and mitofusion 2 (Mfn2) is crucial for the activation of myoblast differentiation. In the present study, we investigated the interplay between the Hippo-Yap pathway and protein contents of Mfn2 and Drp1 during myoblast differentiation...
June 13, 2018: American Journal of Physiology. Cell Physiology
Xiaotao Xu, Qingwei Zhu, Fangfang Niu, Rong Zhang, Yan Wang, Wenying Wang, Dawei Sun, Xintao Wang, Aizhong Wang
The epithelial barrier of the lung is destroyed during acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) due to the apoptosis of alveolar epithelial cells (AECs). Therefore, treatments that block AEC apoptosis might be a therapeutic strategy to ameliorate ALI. Based on recent evidence, A2B adenosine receptor (A2BAR) plays an important role in ALI in several different animal models, but its exact function in AECs has not been clarified. We investigated the role of A2BAR in AEC apoptosis in a mouse model of oleic acid (OA)-induced ALI and in hydrogen peroxide (H2 O2 )-induced AEC (A549 cells and MLE-12 cells) injury...
June 13, 2018: American Journal of Physiology. Cell Physiology
Dandan Zong, Jinhua Li, Shan Cai, Shengdong He, Qingqing Liu, Jiehan Jiang, Shanshan Chen, Yingjiao Long, Yan Chen, Ping Chen, Ruoyun Ouyang
Notch signaling is a critical cell fate determinant of proliferation, differentiation, and apoptosis. In this current study we aimed to investigate whether Notch signaling is involved in cigarette smoke (CS) induced endothelial apoptosis in COPD. Surgical specimens were obtained from 10 patients with COPD and 10 control participants. Notch1, 2, 4 were expressed in endothelial cells, whereas, Notch3 was mainly localized in smooth muscle cells. Decreased Notch1, 3, 4 and the target gene Hes1 and Hes2, increased Notch2 and extracellular signal-regulated kinase (ERK)1/2 were found in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE)...
June 6, 2018: American Journal of Physiology. Cell Physiology
Rosana I Reis, Marie D Nogueira, Ana Lucia Campanha-Rodrigues, Larissa Miranda Pereira, Maria Claudina C Andrade, Lucas T Parreiras-E-Silva, Claudio M Costa Neto, Renato Arruda Mortara, Dulce E Casarini
Hypertension is a global health problem and ACE inhibitors are largely used to control this pathology. Recently, it has been shown that ACE can also act as a transducer signal molecule when its inhibitors or substrates bind to it. This new role of ACE could contribute to understanding some of the effects not explained by its catalytic activity only. In this study we investigated signaling pathways activation in Chinese hamster ovary (CHO) cells stably expressing ACE (CHO-ACE) under different treatments. We also investigated gene modulation after 4h and 24h captopril treatments...
June 6, 2018: American Journal of Physiology. Cell Physiology
Tohru Fukai, Masuko Ushio-Fukai, Jack H Kaplan
Copper (Cu) is an essential micronutrient but excess Cu is potentially toxic. Its important propensity to cycle between two oxidation states accounts for its frequent presence as a co-factor in many physiological processes through Cu-containing enzymes, including mitochondrial energy production (via cytochrome c oxidase), protection against oxidative stress (via superoxide dismutase), and extracellular matrix stability (via lysyl oxidase). Since free Cu is potentially toxic, the bioavailability of intracellular Cu is tightly controlled by Cu transporters and Cu chaperones...
June 6, 2018: American Journal of Physiology. Cell Physiology
Xu Cao, Bikash R Pattnaik, Bret A Hughes
The basolateral membrane anion conductance of the retinal pigment epithelium (RPE) is a key component of the transepithelial Cl- transport pathway. Although multiple Cl- channels have been found to be expressed in the RPE, the components of the resting Cl- conductance have not been identified. In this study, we used the patch-clamp method to characterize the ion selectivity of the anion conductance in isolated mouse RPE cells and in excised patches of RPE basolateral and apical membranes. Relative permeabilities (PA /PCl ) calculated from reversal potentials measured in whole-cell recordings under bi-ionic conditions were as follows: SCN- > ClO4 - > NO3 - > I- > Br- > Cl- > gluconate...
June 6, 2018: American Journal of Physiology. Cell Physiology
Mariela Arias-Hidalgo, Samer Al-Samir, Gerolf Gros, Volker Endeward
We present here a compilation of membrane CO2 permeabilities (PCO2 ) for various cell types from the literature. PCO2 values vary over more than two orders of magnitude. Relating PCO2 to the cholesterol content of the membranes shows that, with the exception of red blood cells, it is essentially membrane cholesterol that determines the value of PCO2 . Thus, the observed strong modulation of PCO2 in the majority of membranes is caused by cholesterol rather than gas channels.
June 6, 2018: American Journal of Physiology. Cell Physiology
Sahar Bilal, Shirin Jaggi, Danielle Janosevic, Nikita Shah, Shereen Teymour, Angelina Voronina, Jessica Watari, Josephine Axis, Kurt Amsler
Hydrogen peroxide (H2 O2 ) increases paracellular permeability of MDCK cells but the mechanism mediating this effect remains unclear. Treatment of MDCK cells with H2 O2 activated ERK 1/2. Inhibition of ERK 1/2 activation blocked the ability of H2 O2 to increase paracellular permeability. Knockdown of ZO-1 protein, but not occludin, eliminated the ability of H2 O2 to increase paracellular permeability. H2 O2 treatment did not, however, affect the total cell content or contents of the Triton X-100-soluble and -insoluble fractions for occludin, ZO-1 or ZO-2...
June 6, 2018: American Journal of Physiology. Cell Physiology
Sarah M Gray, Eugene J Barrett
While there is a growing consensus that insulin has diverse and important regulatory actions on the brain, seemingly important aspects of brain insulin physiology are poorly understood. Examples include: what is the insulin concentration within brain interstitial fluid under normal physiologic conditions; whether insulin is made in the brain and acts locally; does insulin from the circulation cross the blood-brain barrier or the blood-CSF barrier in a fashion that facilitates its signaling in brain; is insulin degraded within the brain; do privileged areas with a "leaky" blood-brain barrier serve as signaling nodes for transmitting peripheral insulin signaling; does insulin action in the brain include regulation of amyloid peptides; whether insulin resistance is a cause or consequence of processes involved in cognitive decline...
May 30, 2018: American Journal of Physiology. Cell Physiology
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