Oxidative stress destabilizes protein arginine methyltransferase 4 via glycogen synthase kinase 3{beta} to impede lung epithelial cell migration
Oxidative stress impacts normal cellular function leading to the pathogenesis of various diseases including pulmonary illnesses. Protein arginine methyltransferase 4 (PRMT4) is critical for normal lung alveolar epithelial cell development; however, the regulation of PRMT4 within such pulmonary diseases has yet to be elucidated. Using biochemical approaches, we uncovered that peroxide (H2O2) treatment decreases PRMT4 protein stability in murine lung epithelial (MLE12) cells to impede cell migration. Protein kinase glycogen synthase kinase 3β (GSK-3β) interacts with PRMT4 and catalyzes PRMT4 T132 phosphorylation th...
Source: AJP: Cell Physiology - September 1, 2017 Category: Cytology Authors: Li, X., Lai, Y., Li, J., Zou, M., Zou, C. Tags: RESEARCH ARTICLE Source Type: research

Characterization of ectonucleotidase expression in the rat carotid body: regulation by chronic hypoxia
The carotid body (CB) chemoreflex maintains blood Po2 and Pco2/H+ homeostasis and displays sensory plasticity during exposure to chronic hypoxia. Purinergic signaling via P1 and P2 receptors plays a pivotal role in shaping the afferent discharge at the sensory synapse containing catecholaminergic chemoreceptor (type I) cells, glial-like type II cells, and sensory (petrosal) nerve endings. However, little is known about the family of ectonucleotidases that control synaptic nucleotide levels. Using quantitative PCR (qPCR), we first compared expression levels of ectonucleoside triphosphate diphosphohydrolases (NTPDases1,2,3,5...
Source: AJP: Cell Physiology - September 1, 2017 Category: Cytology Authors: Salman, S., Vollmer, C., McClelland, G. B., Nurse, C. A. Tags: RESEARCH ARTICLE Source Type: research

Myoendothelial gap junctions mediate regulation of angiopoietin-2-induced vascular hyporeactivity after hypoxia through connexin 43-gated cAMP transfer
Angiopoietin-2 (Ang-2) contributes to vascular hyporeactivity after hemorrhagic shock and hypoxia through upregulation of inducible nitric oxide synthase (iNOS) in a vascular endothelial cell (VEC)-specific and Ang-2/Tie2 receptor-dependent manner. While iNOS is primarily expressed in vascular smooth muscle cells (VSMCs), the mechanisms of signal transfer from VECs to VSMCs are unknown. A double-sided coculture model with VECs and VSMCs from Sprague-Dawley rats was used to investigate the role of myoendothelial gap junctions (MEGJs), the connexin (Cx) isoforms involved, and other relevant mechanisms. After hypoxia, VSMCs t...
Source: AJP: Cell Physiology - September 1, 2017 Category: Cytology Authors: Xu, J., Yang, G., Li, T., Liu, L. Tags: RESEARCH ARTICLE Source Type: research

Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3
Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth. In contrast to previous work, two different resistance exercise protocols did not ch...
Source: AJP: Cell Physiology - September 1, 2017 Category: Cytology Authors: Perez-Schindler, J., Esparza, M. C., McKendry, J., Breen, L., Philp, A., Schenk, S. Tags: RAPID REPORT Source Type: research

Defining the STATus quo in muscle hypertrophy. Focus on "Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - September 1, 2017 Category: Cytology Authors: Amorese, A. J., Spangenburg, E. E. Tags: EDITORIAL FOCUS Source Type: research

Regulation of the unfolded protein response by noncoding RNA
Cells are exposed to various intrinsic and extrinsic stresses in both physiological and pathological conditions. To adapt to those conditions, cells have evolved various mechanisms to cope with the disturbances in protein demand, largely through the unfolded protein response (UPR) in the endoplasmic reticulum (ER), but also through the integrated stress response (ISR). Both responses initiate downstream signaling to transcription factors that, in turn, trigger adaptive programs and/or in the case of prolonged stress, cell death mechanisms. Recently, noncoding RNAs, including microRNA and long noncoding RNA, have emerged as...
Source: AJP: Cell Physiology - September 1, 2017 Category: Cytology Authors: McMahon, M., Samali, A., Chevet, E. Tags: REVIEW Source Type: research

Is FoxO1 the culprit, partner in crime, or a protector in systemic inflammation?
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - August 3, 2017 Category: Cytology Authors: Sundaresan, S., Puthanveetil, P. Tags: VIEWPOINT Source Type: research

Structure/functional aspects of the human riboflavin transporter-3 (SLC52A3): role of the predicted glycosylation and substrate-interacting sites
This study also identified a number of residues in the hRFVT-3 polypeptide that are important for its function/cell surface expression. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - August 3, 2017 Category: Cytology Authors: Subramanian, V. S., Sabui, S., Teafatiller, T., Bohl, J. A., Said, H. M. Tags: RESEARCH ARTICLE Source Type: research

Recruitment of endosomal signaling mediates the forskolin modulation of guinea pig cardiac neuron excitability
Forskolin, a selective activator of adenylyl cyclase (AC), commonly is used to establish actions of G protein-coupled receptors (GPCRs) that are initiated primarily through activation of AC/cAMP signaling pathways. In the present study, forskolin was used to evaluate the potential role of AC/cAMP, which is a major signaling mechanism for the pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor, in the regulation of guinea pig cardiac neuronal excitability. Forskolin (5–10 µM) increases excitability in ~60% of the cardiac neurons. The forskolin-mediated increase in excitability was ...
Source: AJP: Cell Physiology - August 3, 2017 Category: Cytology Authors: Hardwick, J. C., Clason, T. A., Tompkins, J. D., Girard, B. M., Baran, C. N., Merriam, L. A., May, V., Parsons, R. L. Tags: RESEARCH ARTICLE Source Type: research

Chronic hypoxia alters fetal cerebrovascular responses to endothelin-1
In utero hypoxia influences the structure and function of most fetal arteries, including those of the developing cerebral circulation. Whereas the signals that initiate this hypoxic remodeling remain uncertain, these appear to be distinct from the mechanisms that maintain the remodeled vascular state. The present study explores the hypothesis that chronic hypoxia elicits sustained changes in fetal cerebrovascular reactivity to endothelin-1 (ET-1), a potent vascular contractant and mitogen. In fetal lambs, chronic hypoxia (3,820-m altitude for the last 110 days of gestation) had no significant effect on plasma ET-1 levels o...
Source: AJP: Cell Physiology - August 3, 2017 Category: Cytology Authors: Silpanisong, J., Kim, D., Williams, J. M., Adeoye, O. O., Thorpe, R. B., Pearce, W. J. Tags: RESEARCH ARTICLE Source Type: research

Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in renal proximal tubule cells from rat models of hypertension: aged F344 rats and spontaneously hypertensive rats
Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells, dopamine decreases NHERF-1 association with NKA α1 but increases its association with D1R. However, it is not known whether NHERF-1 plays a role i...
Source: AJP: Cell Physiology - August 3, 2017 Category: Cytology Authors: Barati, M. T., Ketchem, C. J., Merchant, M. L., Kusiak, W. B., Jose, P. A., Weinman, E. J., LeBlanc, A. J., Lederer, E. D., Khundmiri, S. J. Tags: RESEARCH ARTICLE Source Type: research

The activation of N-methyl-D-aspartate receptors downregulates transient outward potassium and L-type calcium currents in rat models of depression
Major depression is an important clinical factor in ventricular arrhythmia. Patients diagnosed with major depression overexpress N-methyl-d-aspartate receptors (NMDARs). Previous studies found that chronic NMDAR activation increases susceptibility to ventricular arrhythmias. We aimed to explore the mechanisms by which NMDAR activation may increase susceptibility to ventricular arrhythmias. Male rats were randomly assigned to either normal environments as control (CTL) group or 4 wk of chronic mild stress (CMS) to produce a major depression disorder (MDD) model group. After 4 wk of CMS, depression-like behaviors were measur...
Source: AJP: Cell Physiology - August 3, 2017 Category: Cytology Authors: Liu, X., Shi, S., Yang, H., Qu, C., Chen, Y., Liang, J., Yang, B. Tags: RESEARCH ARTICLE Source Type: research

The NH2 terminus regulates voltage-dependent gating of CALHM ion channels
Calcium homeostasis modulator protein-1 (CALHM1) and its Caenorhabditis elegans (ce) homolog, CLHM-1, belong to a new family of physiologically important ion channels that are regulated by voltage and extracellular Ca2+ (Ca2+o) but lack a canonical voltage-sensing domain. Consequently, the intrinsic voltage-dependent gating mechanisms for CALHM channels are unknown. Here, we performed voltage-clamp experiments on ceCLHM-1 chimeric, deletion, insertion, and point mutants to assess the role of the NH2 terminus (NT) in CALHM channel gating. Analyses of chimeric channels in which the ceCLHM-1 and human (h)CALHM1 NH2 termini we...
Source: AJP: Cell Physiology - August 1, 2017 Category: Cytology Authors: Tanis, J. E., Ma, Z., Foskett, J. K. Tags: RESEARCH ARTICLE Source Type: research

Estradiol activates chloride channels via estrogen receptor-{alpha} in the cell membranes of osteoblasts
In conclusion, our findings show that Cl– channels can be activated by estrogen via ERα on the cell membrane and suggest that the ClC-3 Cl– channel may be one of the targets of estrogen in the regulation of osteoblast activity. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - August 1, 2017 Category: Cytology Authors: Deng, Z., Peng, S., Zheng, Y., Yang, X., Zhang, H., Tan, Q., Liang, X., Gao, H., Li, Y., Huang, Y., Zhu, L., Jacob, T. J. C., Chen, L., Wang, L. Tags: RESEARCH ARTICLE Source Type: research

Effects of sarcolipin deletion on skeletal muscle adaptive responses to functional overload and unload
Overexpression of sarcolipin (SLN), a regulator of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs), stimulates calcineurin signaling to enhance skeletal muscle oxidative capacity. Some studies have shown that calcineurin may also control skeletal muscle mass and remodeling in response to functional overload and unload stimuli by increasing myofiber size and the proportion of slow fibers. To examine whether SLN might mediate these adaptive responses, we performed soleus and gastrocnemius tenotomy in wild-type (WT) and Sln-null (Sln–/–) mice and examined the overloaded plantaris and unloaded/tenotomized soleus...
Source: AJP: Cell Physiology - August 1, 2017 Category: Cytology Authors: Fajardo, V. A., Rietze, B. A., Chambers, P. J., Bellissimo, C., Bombardier, E., Quadrilatero, J., Tupling, A. R. Tags: RESEARCH ARTICLE Source Type: research