The unfolded protein response in relation to mitochondrial biogenesis in skeletal muscle cells
Mitochondria comprise both nuclear and mitochondrially encoded proteins requiring precise stoichiometry for their integration into functional complexes. The augmented protein synthesis associated with mitochondrial biogenesis results in the accumulation of unfolded proteins, thus triggering cellular stress. As such, the unfolded protein responses emanating from the endoplasmic reticulum (UPRER) or the mitochondrion (UPRMT) are triggered to ensure correct protein handling. Whether this response is necessary for mitochondrial adaptations is unknown. Two models of mitochondrial biogenesis were used: muscle differentiation and...
Source: AJP: Cell Physiology - May 3, 2017 Category: Cytology Authors: Mesbah Moosavi, Z. S., Hood, D. A. Tags: ARTICLES Source Type: research
Erythropoietin facilitates definitive endodermal differentiation of mouse embryonic stem cells via activation of ERK signaling
This study suggests a possible role of EPO in embryonic endodermal development and a new agent for directing the differentiation into endodermal lineages like pancreatic β-cells. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - May 1, 2017 Category: Cytology Authors: Kaitsuka, T., Kobayashi, K., Otsuka, W., Kubo, T., Hakim, F., Wei, F.-Y., Shiraki, N., Kume, S., Tomizawa, K. Tags: RESEARCH ARTICLE Source Type: research
TRPV4 ion channel is a novel regulator of dermal myofibroblast differentiation
The objective of this study was to determine the role of TRPV4 in TGFβ1- and matrix stiffness-induced differentiation of dermal fibroblasts. We found that TRPV4 channels are expressed and functional in both human (HDF) and mouse (MDF) dermal fibroblasts. TRPV4 activity (agonist-induced Ca2+ influx) was induced by both matrix stiffness and TGFβ1 in dermal fibroblasts. TGFβ1 induced expression of TRPV4 proteins in a dose-dependent manner. Genetic ablation or pharmacological antagonism of TRPV4 channel abrogated Ca2+ influx and both TGFβ1-induced and matrix stiffness-induced myofibroblast differentiation a...
Source: AJP: Cell Physiology - May 1, 2017 Category: Cytology Authors: Sharma, S., Goswami, R., Merth, M., Cohen, J., Lei, K. Y., Zhang, D. X., Rahaman, S. O. Tags: RESEARCH ARTICLE Source Type: research
Identification of a mammalian silicon transporter
Silicon (Si) has long been known to play a major physiological and structural role in certain organisms, including diatoms, sponges, and many higher plants, leading to the recent identification of multiple proteins responsible for Si transport in a range of algal and plant species. In mammals, despite several convincing studies suggesting that silicon is an important factor in bone development and connective tissue health, there is a critical lack of understanding about the biochemical pathways that enable Si homeostasis. Here we report the identification of a mammalian efflux Si transporter, namely Slc34a2 (also termed Na...
Source: AJP: Cell Physiology - May 1, 2017 Category: Cytology Authors: Ratcliffe, S., Jugdaohsingh, R., Vivancos, J., Marron, A., Deshmukh, R., Ma, J. F., Mitani-Ueno, N., Robertson, J., Wills, J., Boekschoten, M. V., Müller, M., Mawhinney, R. C., Kinrade, S. D., Isenring, P., Belanger, R. R., Powell, J. J. Tags: RESEARCH ARTICLE Source Type: research
Vascular biology of hydrogen sulfide
Hydrogen sulfide (H2S) is a ubiquitous signaling molecule with important functions in many mammalian organs and systems. Observations in the 1990s ascribed physiological actions to H2S in the nervous system, proposing that this gasotransmitter acts as a neuromodulator. Soon after that, the vasodilating properties of H2S were demonstrated. In the past decade, H2S was shown to exert a multitude of physiological effects in the vessel wall. H2S is produced by vascular cells and exhibits antioxidant, antiapoptotic, anti-inflammatory, and vasoactive properties. In this concise review, we have focused on the impact of H2S on vasc...
Source: AJP: Cell Physiology - May 1, 2017 Category: Cytology Authors: Kanagy, N. L., Szabo, C., Papapetropoulos, A. Tags: THEME Source Type: research
Assessment of roles for the Rho-specific guanine nucleotide dissociation inhibitor Ly-GDI in platelet function: a spatial systems approach
On activation at sites of vascular injury, platelets undergo morphological alterations essential to hemostasis via cytoskeletal reorganizations driven by the Rho GTPases Rac1, Cdc42, and RhoA. Here we investigate roles for Rho-specific guanine nucleotide dissociation inhibitor proteins (RhoGDIs) in platelet function. We find that platelets express two RhoGDI family members, RhoGDI and Ly-GDI. Whereas RhoGDI localizes throughout platelets in a granule-like manner, Ly-GDI shows an asymmetric, polarized localization that largely overlaps with Rac1 and Cdc42 as well as microtubules and protein kinase C (PKC) in platelets adher...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Ngo, A. T. P., Thierheimer, M. L. D., Babur, O., Rocheleau, A. D., Huang, T., Pang, J., Rigg, R. A., Mitrugno, A., Theodorescu, D., Burchard, J., Nan, X., Demir, E., McCarty, O. J. T., Aslan, J. E. Tags: RESEARCH ARTICLE Source Type: research
Impact of posttranslational modifications of engineered cysteines on the substituted cysteine accessibility method: evidence for glutathionylation
The substituted cysteine accessibility method (SCAM) is widely used to study the structure and function of channels, receptors and transporters. In its usual application, a cysteine residue is introduced into a protein which lacks native cysteines following which the accessibility of the residue to the aqueous compartment is assessed. Implicit, and generally assumed, is that if the cysteine-substituted residue is not available to react with sulfhydryl reagents it is not exposed to the extracellular compartment or within the aqueous translocation pathway. We demonstrate here, in a Hela-derived cell line, that some cysteine-...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Zhao, R., Najmi, M., Aluri, S., Goldman, I. D. Tags: RESEARCH ARTICLE Source Type: research
Triglyceride-rich lipoprotein lipolysis products increase blood-brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress
Elevation of blood triglycerides, primarily as triglyceride-rich lipoproteins (TGRL), has been linked to cerebrovascular inflammation, vascular dementia, and Alzheimer’s disease (AD). Brain microvascular endothelial cells and astrocytes, two cell components of the neurovascular unit, participate in controlling blood-brain barrier (BBB) permeability and regulating neurovascular unit homeostasis. Our studies showed that infusion of high physiological concentrations of TGRL lipolysis products (TGRL + lipoprotein lipase) activate and injure brain endothelial cells and transiently increase the BBB transfer coefficient (Ki...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Lee, L. L., Aung, H. H., Wilson, D. W., Anderson, S. E., Rutledge, J. C., Rutkowsky, J. M. Tags: RESEARCH ARTICLE Source Type: research
Zinc suppresses stem cell properties of lung cancer cells through protein kinase C-mediated {beta}-catenin degradation
Highly tumorigenic cancer stem cells (CSCs) residing in most cancers are responsible for cancer progression and treatment failure. Zinc is an element regulator of several cell functions; however, its role in regulation of stem cell program in lung cancer has not been demonstrated. The present study reveals for the first time that zinc can suppress stem cell properties of lung cancer cells. Such findings were proved in different lung cancer cell lines (H460, H23, and H292) and it was found that CSC markers (CD133 and ALDH1A1), stem cell-associated transcription factors (Oct4, Nanog, and Sox-2), and the ability to form tumor...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Ninsontia, C., Phiboonchaiyanan, P. P., Kiratipaiboon, C., Chanvorachote, P. Tags: RESEARCH ARTICLE Source Type: research
Absence of suppressor of cytokine signaling 2 turns cardiomyocytes unresponsive to LIF-dependent increases in Ca2+ levels
Little is known regarding the role of suppressor of cytokine signaling (SOCS) in the control of cytokine signaling in cardiomyocytes. We investigated the consequences of SOCS2 ablation for leukemia inhibitory factor (LIF)-induced enhancement of intracellular Ca2+ ([Ca2+]i) transient by performing experiments with cardiomyocytes from SOCS2-knockout (ko) mice. Similar levels of SOCS3 transcripts were seen in cardiomyocytes from wild-type and SOCS2-ko mice, while SOCS1 mRNA was reduced in SOCS2-ko. Immunoprecipitation experiments showed increased SOCS3 association with gp130 receptor in SOCS2-ko myocytes. Measurements of Ca2+...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Rocha-Resende, C., Guedes de Jesus, I. C., Roman-Campos, D., Miranda, A. S., Alves, F., Resende, R. R., dos Santos Cruz, J., Machado, F. S., Guatimosim, S. Tags: RESEARCH ARTICLE Source Type: research
Caveolins and cavins in the trafficking, maturation, and degradation of caveolae: implications for cell physiology
Caveolins (Cavs) are ~20 kDa scaffolding proteins that assemble as oligomeric complexes in lipid raft domains to form caveolae, flask-shaped plasma membrane (PM) invaginations. Caveolae ("little caves") require lipid-lipid, protein-lipid, and protein-protein interactions that can modulate the localization, conformational stability, ligand affinity, effector specificity, and other functions of proteins that are partners of Cavs. Cavs are assembled into small oligomers in the endoplasmic reticulum (ER), transported to the Golgi for assembly with cholesterol and other oligomers, and then exported to the PM as an intact coat c...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Busija, A. R., Patel, H. H., Insel, P. A. Tags: REVIEW Source Type: research
Kinetic analyses of vasculogenesis inform mechanistic studies
Vasculogenesis is a complex process by which endothelial stem and progenitor cells undergo de novo vessel formation. Quantitative assessment of vasculogenesis is a central readout of endothelial progenitor cell functionality. However, current assays lack kinetic measurements. To address this issue, new approaches were developed to quantitatively assess in vitro endothelial colony-forming cell (ECFC) network formation in real time. Eight parameters of network structure were quantified using novel Kinetic Analysis of Vasculogenesis (KAV) software. KAV assessment of structure complexity identified two phases of network format...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Varberg, K. M., Winfree, S., Chu, C., Tu, W., Blue, E. K., Gohn, C. R., Dunn, K. W., Haneline, L. S. Tags: METHODS IN CELL PHYSIOLOGY Source Type: research
Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions
The objective of the present study was to delineate the underlying mechanisms. The human IEC lines Caco-2 and HT-29 were used for these studies and modulation of direct as well as indirect effects of LPS on intracellular signaling as well as tight junctions were examined. Pretreatment with curcumin significantly attenuated LPS-induced secretion of master cytokine IL-1β from IECs and macrophages. Furthermore, curcumin also reduced IL-1β-induced activation of p38 MAPK in IECs and subsequent increase in expression of myosin light chain kinase involved in the phosphorylation of tight junction proteins and ensuing dis...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Wang, J., Ghosh, S. S., Ghosh, S. Tags: RESEARCH ARTICLE Source Type: research
Shear stress induces G{alpha}q/11 activation independently of G protein-coupled receptor activation in endothelial cells
In this study, we used in situ proximity ligation assay (PLA) to investigate the role of a specific GPCR/Gαq/11 pair in EC shear stress-induced mechanotransduction. We demonstrated that sphingosine 1-phosphate (S1P) stimulation causes a rapid dissociation at 0.5 min of Gαq/11 from its receptor S1P3, followed by an increased association within 2 min of GPCR kinase-2 (GRK2) and β-arrestin-1/2 with S1P3 in human coronary artery ECs, which are consistent with GPCR/Gαq/11 activation and receptor desensitization/internalization. The G protein activator AlF4 resulted in increased dissociation of Gαq/1...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: dela Paz, N. G., Melchior, B., Frangos, J. A. Tags: RESEARCH ARTICLE Source Type: research
Doxorubicin-induced nitrosative stress is mitigated by vitamin C via the modulation of nitric oxide synthases
An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox)–induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms, and nitrosative stress as well as cytokines TN...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Akolkar, G., Bagchi, A. K., Ayyappan, P., Jassal, D. S., Singal, P. K. Tags: RESEARCH ARTICLE Source Type: research
