Insulin and SGK1 reduce the function of Na+/monocarboxylate transporter 1 (SMCT1/SLC5A8)
SMCTs move several important fuel molecules that are involved in lipid, carbohydrate, and amino acid metabolism, but their regulation has been poorly studied. Insulin controls the translocation of several solutes that are involved in energetic cellular metabolism, including glucose. We studied the effect of insulin on the function of human SMCT1 expressed in Xenopus oocytes. The addition of insulin reduced α-keto-isocaproate (KIC)-dependent 22Na+ uptake by 29%. Consistent with this result, the coinjection of SMCT1 with SGK1 cRNA decreased the KIC-dependent 22Na+ uptake by 34%. The reduction of SMCT1 activity by SGK1 ...
Source: AJP: Cell Physiology - October 31, 2016 Category: Cytology Authors: Lopez-Barradas, A., Gonzalez-Cid, T., Vazquez, N., Gavi-Maza, M., Reyes-Camacho, A., Velazquez-Villegas, L. A., Ramirez, V., Zandi-Nejad, K., Mount, D. B., Torres, N., Tovar, A. R., Romero, M. F., Gamba, G., Plata, C. Tags: ARTICLES Source Type: research
sFRP2 activates Wnt/{beta}-catenin signaling in cardiac fibroblasts: differential roles in cell growth, energy metabolism, and extracellular matrix remodeling
Secreted Frizzled-related protein 2 (sFRP2) plays a key role in chronic fibrosis after myocardial infarction and in heart failure. The aim of this study was to elucidate the mechanisms through which sFRP2 may regulate the growth and extracellular matrix (ECM) remodeling of adult mouse cardiac fibroblasts (CFs). We found that sFRP2 activates CFs in part through canonical Wnt/β-catenin signaling, as evidenced by increased expression of Axin2 and Wnt3a, but not Wnt5a, as well as accumulation of nuclear β-catenin. In response to sFRP2, CFs exhibited robust cell proliferation associated with increased glucose consumpt...
Source: AJP: Cell Physiology - October 31, 2016 Category: Cytology Authors: Lin, H., Angeli, M., Chung, K. J., Ejimadu, C., Rosa, A. R., Lee, T. Tags: CALL FOR PAPERS Source Type: research
cAMP-dependent recruitment of acidic organelles for Ca2+ signaling in the salivary gland
Autonomic neural activation of intracellular Ca2+ release in parotid acinar cells induces the secretion of the fluid and protein components of primary saliva critical for maintaining overall oral homeostasis. In the current study, we profiled the role of acidic organelles in shaping the Ca2+ signals of parotid acini using a variety of imaging and pharmacological approaches. Results demonstrate that zymogen granules predominate as an apically polarized population of acidic organelles that contributes to the initial Ca2+ release. Moreover, we provide evidence that indicates a role for the intracellular messenger NAADP in the...
Source: AJP: Cell Physiology - October 31, 2016 Category: Cytology Authors: Imbery, J. F., Bhattacharya, S., Khuder, S., Weiss, A., Goswamee, P., Iqbal, A. K., Giovannucci, D. R. Tags: CALL FOR PAPERS Source Type: research
High potassium promotes mutual interaction between (pro)renin receptor and the local renin-angiotensin-aldosterone system in rat inner medullary collecting duct cells
(Pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD) with unclear functional implication. It is not known whether CD PRR is regulated by high potassium (HK). Here, we aimed to investigate the effect of HK on PRR expression and its role in regulation of aldosterone synthesis and release in the CD. In primary rat inner medullary CD cells, HK augmented PRR expression and soluble PPR (sPRR) release in a time- and dose-dependent manner, which was attenuated by PRR small interfering RNA (siRNA), eplerenone, and losartan. HK upregulated aldosterone release in parallel with an increase of CYP11B2 (cytoc...
Source: AJP: Cell Physiology - October 9, 2016 Category: Cytology Authors: Xu, C., Fang, H., Zhou, L., Lu, A., Yang, T. Tags: ARTICLES Source Type: research
Deletion of calponin 2 in macrophages attenuates the severity of inflammatory arthritis in mice
Calponin is an actin cytoskeleton-associated protein that regulates motility-based cellular functions. Three isoforms of calponin are present in vertebrates, among which calponin 2 encoded by the Cnn2 gene is expressed in multiple types of cells, including blood cells from the myeloid lineage. Our previous studies demonstrated that macrophages from Cnn2 knockout (KO) mice exhibit increased migration and phagocytosis. Intrigued by an observation that monocytes and macrophages from patients with rheumatoid arthritis had increased calponin 2, we investigated anti-glucose-6-phosphate isomerase serum-induced arthritis in Cnn2-K...
Source: AJP: Cell Physiology - October 9, 2016 Category: Cytology Authors: Huang, Q.-Q., Hossain, M. M., Sun, W., Xing, L., Pope, R. M., Jin, J.- P. Tags: ARTICLES Source Type: research
mTOR signaling regulates myotube hypertrophy by modulating protein synthesis, rDNA transcription, and chromatin remodeling
Ribosome production is an early event during skeletal muscle hypertrophy and precedes muscle protein accretion. Signaling via mTOR is crucial for ribosome production and hypertrophy; however, the mechanisms by which it regulates these processes remain to be identified. Herein, we investigated the activation of mTOR signaling in hypertrophying myotubes and determined that mTOR coordinates various aspects of gene expression important for ribosome production. First, inhibition of translation with cycloheximide had a more potent effect on protein synthesis than rapamycin indicating that mTOR function during hypertrophy is not ...
Source: AJP: Cell Physiology - October 9, 2016 Category: Cytology Authors: von Walden, F., Liu, C., Aurigemma, N., Nader, G. A. Tags: CALL FOR PAPERS Source Type: research
Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton
Vitamin C, or ascorbic acid, both tightens the endothelial permeability barrier in basal cells and also prevents barrier leak induced by inflammatory agents. Barrier tightening by ascorbate in basal endothelial cells requires nitric oxide derived from activation of nitric oxide synthase. Although ascorbate did not affect cyclic AMP levels in our previous study, there remains a question of whether it might activate downstream cyclic AMP-dependent pathways. In this work, we found in both primary and immortalized cultured endothelial cells that ascorbate tightened the endothelial permeability barrier by ~30%. In human umbilic...
Source: AJP: Cell Physiology - October 9, 2016 Category: Cytology Authors: Parker, W. H., Rhea, E. M., Qu, Z.-C., Hecker, M. R., May, J. M. Tags: CALL FOR PAPERS Source Type: research
Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability
Pituitary adenylate cyclase (PAC)-activating polypeptide (PACAP) peptides (Adcyap1) signaling at the selective PAC1 receptor (Adcyap1r1) participate in multiple homeostatic and stress-related responses, yet the cellular mechanisms underlying PACAP actions remain to be completely elucidated. PACAP/PAC1 receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia, and as these neurons are readily accessible, this neuronal system is particularly amenable to study of PACAP modulation of ionic conductances. The present study investigated how PACAP activation of MEK/ERK signaling contributed to the ...
Source: AJP: Cell Physiology - October 9, 2016 Category: Cytology Authors: Tompkins, J. D., Clason, T. A., Hardwick, J. C., Girard, B. M., Merriam, L. A., May, V., Parsons, R. L. Tags: CALL FOR PAPERS Source Type: research
NaV-igating the MAP from PACAP to excitement. Focus on "Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 9, 2016 Category: Cytology Authors: Currie, K. P. M. Tags: EDITORIAL FOCUS Source Type: research
PIP2 in pancreatic {beta}-cells regulates voltage-gated calcium channels by a voltage-independent pathway
Phosphatidylinositol-4,5-bisphosphate (PIP2) is a membrane phosphoinositide that regulates the activity of many ion channels. Influx of calcium primarily through voltage-gated calcium (CaV) channels promotes insulin secretion in pancreatic β-cells. However, whether CaV channels are regulated by PIP2, as is the case for some non-insulin-secreting cells, is unknown. The purpose of this study was to investigate whether CaV channels are regulated by PIP2 depletion in pancreatic β-cells through activation of a muscarinic pathway induced by oxotremorine methiodide (Oxo-M). CaV channel currents were recorded by the patc...
Source: AJP: Cell Physiology - September 30, 2016 Category: Cytology Authors: de la Cruz, L., Puente, E. I., Reyes-Vaca, A., Arenas, I., Garduno, J., Bravo-Martinez, J., Garcia, D. E. Tags: ARTICLES Source Type: research
Increased hypertrophic response with increased mechanical load in skeletal muscles receiving identical activity patterns
It is often assumed that mechanical factors are important for effects of exercise on muscle, but during voluntary training and most experimental conditions the effects could solely be attributed to differences in electrical activity, and direct evidence for a mechanosensory pathway has been scarce. We here show that, in rat muscles stimulated in vivo under deep anesthesia with identical electrical activity patterns, isometric contractions induced twofold more hypertrophy than contractions with 50–60% of the isometric force. The number of myonuclei and the RNA levels of myogenin and myogenic regulatory factor 4 were i...
Source: AJP: Cell Physiology - September 30, 2016 Category: Cytology Authors: Eftestol, E., Egner, I. M., Lunde, I. G., Ellefsen, S., Andersen, T., Sjaland, C., Gundersen, K., Bruusgaard, J. C. Tags: ARTICLES Source Type: research
The myonuclear domain is not maintained in skeletal muscle during either atrophy or programmed cell death
Skeletal muscle mass can increase during hypertrophy or decline dramatically in response to normal or pathological signals that trigger atrophy. Many reports have documented that the number of nuclei within these cells is also plastic. It has been proposed that a yet-to-be-defined regulatory mechanism functions to maintain a relatively stable relationship between the cytoplasmic volume and nuclear number within the cell, a phenomenon known as the "myonuclear domain" hypothesis. While it is accepted that hypertrophy is typically associated with the addition of new nuclei to the muscle fiber from stem cells such as satellite...
Source: AJP: Cell Physiology - September 30, 2016 Category: Cytology Authors: Schwartz, L. M., Brown, C., McLaughlin, K., Smith, W., Bigelow, C. Tags: ARTICLES Source Type: research
Toll-like receptor 4 mutation suppresses hyperhomocysteinemia-induced hypertension
In this study we hypothesize that HHcy induces hypertension by TLR-4 activation, which promotes inflammatory cytokine (IL-1β, IL-6, and TNF-α) upregulation and initiation of mitochondria-dependent apoptosis, leading to cell death and chronic vascular inflammation. To test this hypothesis, we used C57BL/6J (WT) mice, cystathionine β-synthase (CBS)-deficient (CBS+/–) mice with genetic mild HHcy, C3H/HeJ (C3H) mice with TLR-4 mutation, and mice with combined genetic HHcy and TLR-4 mutation (CBS+/–/C3H). Ultrasonography of the superior mesenteric artery (SMA) detected an increase in wall-to-lumen ra...
Source: AJP: Cell Physiology - September 30, 2016 Category: Cytology Authors: Familtseva, A., Chaturvedi, P., Kalani, A., Jeremic, N., Metreveli, N., Kunkel, G. H., Tyagi, S. C. Tags: ARTICLES Source Type: research
The potassium channels TASK2 and TREK1 regulate functional differentiation of murine skeletal muscle cells
In conclusion, our findings for the first time demonstrate the functional expression of TASK2 and TREK1 in muscle cells with implications for differentiation processes warranting further investigations in physiologic and pathophysiologic scenarios. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - September 30, 2016 Category: Cytology Authors: Afzali, A. M., Ruck, T., Herrmann, A. M., Iking, J., Sommer, C., Kleinschnitz, C., Preusse, C., Stenzel, W., Budde, T., Wiendl, H., Bittner, S., Meuth, S. G. Tags: CALL FOR PAPERS Source Type: research
Activation of Nrf2 contributes to the protective effect of Exendin-4 against angiotensin II-induced vascular smooth muscle cell senescence
In conclusion, these results provide a mechanistic insight into how Nrf2 signaling mediates the antisenescent and antioxidative effects induced by Exendin-4 in VSMCs. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - September 30, 2016 Category: Cytology Authors: Zhou, T., Zhang, M., Zhao, L., Li, A., Qin, X. Tags: ARTICLES Source Type: research
