Regulation of ATP production: dependence on calcium concentration and respiratory state
We examined the action of varying [Ca2+] over respiratory states ranging 4 to 3 on skeletal muscle mitochondrial respiration, potential, ATP production, and H2O2 production using ADP recycling to clamp external [ADP]. Calcium at 450 nM enhanced respiration in mitochondria energized by the complex I substrates, glutamate/malate (but not succinate), at [ADP] of 4–256 µM, but more substantially at intermediate respiratory states and not at all at state 4. Using varied [Ca2+], we found that the stimulatory effects on respiration and ATP production were most prominent at nanomolar concentrations, but inhibitory at 1...
Source: AJP: Cell Physiology - August 1, 2017 Category: Cytology Authors: Fink, B. D., Bai, F., Yu, L., Sivitz, W. I. Tags: RESEARCH ARTICLE Source Type: research

Sarcomere mechanics in striated muscles: from molecules to sarcomeres to cells
This article reviews these issues, looking into studies that have used intact and permeabilized fibers, myofibrils, isolated sarcomeres, and half-sarcomeres. A common mechanism associated with sarcomere and half-sarcomere length nonuniformities and a Ca2+-induced increase in the stiffness of titin is proposed to explain observations that derive from these studies. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - August 1, 2017 Category: Cytology Authors: Rassier, D. E. Tags: REVIEW Source Type: research

S-nitrosylation/denitrosylation regulates myoblast proliferation. Focus on "Balance between S-nitrosylation and denitrosylation modulates myoblast proliferation independently of soluble guanylyl cyclase activation"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - August 1, 2017 Category: Cytology Authors: Monteiro, H. P., Ogata, F. T. Tags: EDITORIAL FOCUS Source Type: research

CFTR-mediated anion secretion across intestinal epithelium-like Caco-2 monolayer under PTH stimulation is dependent on intermediate conductance K+ channels
In conclusion, PTH requires NHE3 and basolateral K+ channels to induce HCO3– and Cl– secretion, thus explaining how PTH regulated luminal pH balance and pH-dependent absorption of trace minerals. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - July 6, 2017 Category: Cytology Authors: Jantarajit, W., Lertsuwan, K., Teerapornpuntakit, J., Krishnamra, N., Charoenphandhu, N. Tags: RESEARCH ARTICLE Source Type: research

FXYD5 (dysadherin) may mediate metastatic progression through regulation of the {beta}-Na+-K+-ATPase subunit in the 4T1 mouse breast cancer model
In this study, using in vivo 4T1 murine breast cancer model, we found that FXYD5-specific shRNA significantly inhibited lung cancer metastasis, without having a substantial effect on primary tumor growth. Our study reveals that FXYD5 participates in multiple stages of metastatic development and exhibits more than one mode of E-cadherin regulation. We provide the first evidence that FXYD5-related morphological changes are mediated through its interaction with Na+-K+-ATPase. Experiments in cultured 4T1 cells have indicated that FXYD5 expression may downregulate the β1 isoform of the pump. This behavior could have implic...
Source: AJP: Cell Physiology - July 6, 2017 Category: Cytology Authors: Lubarski-Gotliv, I., Dey, K., Kuznetsov, Y., Kalchenco, V., Asher, C., Garty, H. Tags: RESEARCH ARTICLE Source Type: research

Primary cilia control the maturation of tubular lumen in renal collecting duct epithelium
In this study, we assessed the role of primary cilium in branching tubulogenesis and/or lumen development using kidney collecting duct-derived mCCDN21 cells that display spontaneous tubulogenic properties when grown in collagen-Matrigel matrix. Tubulogenesis and branching were not altered when cilium body growth was inhibited by Kif3A or Ift88 silencing. In agreement with the absence of a morphogenetic effect, proliferation and wound-healing assay revealed that neither cell proliferation nor migration were altered by cilium body disruption. The absence of cilium following Kif3A or Ift88 silencing in mCCDN21 cells did not a...
Source: AJP: Cell Physiology - July 6, 2017 Category: Cytology Authors: Ernandez, T., Komarynets, O., Chassot, A., Sougoumarin, S., Soulie, P., Wang, Y., Montesano, R., Feraille, E. Tags: RESEARCH ARTICLE Source Type: research

MiR-9-5p promotes MSC migration by activating {beta}-catenin signaling pathway
Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, w...
Source: AJP: Cell Physiology - July 6, 2017 Category: Cytology Authors: Li, X., He, L., Yue, Q., Lu, J., Kang, N., Xu, X., Wang, H., Zhang, H. Tags: RESEARCH ARTICLE Source Type: research

Airway epithelial anion secretion and barrier function following exposure to fungal aeroallergens: role of oxidative stress
In this study, the effect of Alternaria on ion transport mechanisms underlying mucociliary clearance and airway epithelial barrier function was investigated in human airway epithelial cells. Apical exposure to Alternaria induced an increase in anion secretion that was inhibited by blockers of CFTR and Ca2+-activated Cl– channels. Stimulation of anion secretion was dependent on Ca2+ uptake from the apical solution. Alternaria exposure also produced an increase in reactive oxygen species (ROS) that was blocked by pretreatment with the oxidant scavenger glutathione (GSH). GSH and the NADPH oxidase inhibitor/complex 1 el...
Source: AJP: Cell Physiology - July 1, 2017 Category: Cytology Authors: Zaidman, N. A., OGrady, K. E., Patil, N., Milavetz, F., Maniak, P. J., Kita, H., OGrady, S. M. Tags: RESEARCH ARTICLE Source Type: research

Ablation of S1P3 receptor protects mouse soleus from age-related drop in muscle mass, force, and regenerative capacity
We investigated the effects of S1P3 deficiency on the age-related atrophy, decline in force, and regenerative capacity of soleus muscle from 23-mo-old male (old) mice. Compared with muscle from 5-mo-old (adult) mice, soleus mass and muscle fiber cross-sectional area (CSA) in old wild-type mice were reduced by ~26% and 24%, respectively. By contrast, the mass and fiber CSA of soleus muscle in old S1P3-null mice were comparable to those of adult muscle. Moreover, in soleus muscle of wild-type mice, twitch and tetanic tensions diminished from adulthood to old age. A slowing of contractile properties was also observed in soleu...
Source: AJP: Cell Physiology - July 1, 2017 Category: Cytology Authors: Bondi, M., Germinario, E., Pirazzini, M., Zanetti, G., Cencetti, F., Donati, C., Gorza, L., Betto, R., Bruni, P., Danieli-Betto, D. Tags: RESEARCH ARTICLE Source Type: research

ENaC activity is regulated by calpain-2 proteolysis of MARCKS proteins
We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in the anionic phospholipid phosphate-dependent regulation of the epithelial sodium channel (ENaC). Both MARCKS and ENaC are regulated by proteolysis. Calpains are a family of ubiquitously expressed intracellular Ca2+-dependent cysteine proteases involved in signal transduction. Here we examine the role of calpain-2 in regulating MARCKS and ENaC in cultured renal epithelial cells and in the mouse kidney. Using recombinant fusion proteins, we show that MARCKS, but not the ENaC subunits, are a subst...
Source: AJP: Cell Physiology - July 1, 2017 Category: Cytology Authors: Montgomery, D. S., Yu, L., Ghazi, Z. M., Thai, T. L., Al-Khalili, O., Ma, H.-P., Eaton, D. C., Alli, A. A. Tags: RESEARCH ARTICLE Source Type: research

Melamine induces Ca2+-sensing receptor activation and elicits apoptosis in proximal tubular cells
Melamine causes renal tubular cell injury through inflammation, fibrosis, and apoptosis. Although melamine affects the rise in intracellular Ca2+ concentration ([Ca2+]i), reactive oxygen species (ROS) production, and proapoptotic pathway activation, the mechanism of upstream Ca2+ signaling is unknown. Because melamine has some structural similarities with l-amino acids, which endogenously activate Ca2+-sensing receptors (CSR), we examined the effect of melamine on CSR-induced Ca2+ signaling and apoptotic cell death. We show here that melamine activates CSR, causing a sustained Ca2+ entry in the renal epithelial cell line, ...
Source: AJP: Cell Physiology - July 1, 2017 Category: Cytology Authors: Yiu, A. J., Ibeh, C.-L., Roy, S. K., Bandyopadhyay, B. C. Tags: RESEARCH ARTICLE Source Type: research

Balance between S-nitrosylation and denitrosylation modulates myoblast proliferation independently of soluble guanylyl cyclase activation
Nitric oxide (NO) contributes to myogenesis by regulating the transition between myoblast proliferation and fusion through cGMP signaling. NO can form S-nitrosothiols (RSNO), which control signaling pathways in many different cell types. However, neither the role of RSNO content nor its regulation by the denitrosylase activity of S-nitrosoglutathione reductase (GSNOR) during myogenesis is understood. Here, we used primary cultures of chick embryonic skeletal muscle cells to investigate whether changes in intracellular RSNO alter proliferation and fusion of myoblasts in the presence and absence of cGMP. Cultures were grown ...
Source: AJP: Cell Physiology - July 1, 2017 Category: Cytology Authors: Yamashita, A. M. S., Ancillotti, M. T. C., Rangel, L. P., Fontenele, M., Figueiredo-Freitas, C., Possidonio, A. C., Soares, C. P., Sorenson, M. M., Mermelstein, C., Nogueira, L. Tags: RESEARCH ARTICLE Source Type: research

Applying fluid biomarkers to Alzheimer's disease
Alzheimer’s disease (AD) is a common neurodegenerative disease that starts with a clinically silent phase of a decade or more during which brain pathologies accumulate predominantly in the medial temporal lobe but also elsewhere in the brain. Network dysfunction and clinical symptoms typically appear when senile plaque (amyloid-β) and neurofibrillary tangle (tau) pathologies meet in the brain parenchyma, producing synapse and neuronal loss. For plaque and tangle pathologies, reliable fluid biomarkers have been developed. These require sampling of cerebrospinal fluid. Reliable blood tests for plaque and tangle pa...
Source: AJP: Cell Physiology - July 1, 2017 Category: Cytology Authors: Zetterberg, H. Tags: THEME Source Type: research

Multi-omics and Alzheimers disease: a slower but surer path to an efficacious therapy?
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - July 1, 2017 Category: Cytology Authors: Pimplikar, S. W. Tags: EDITORIAL Source Type: research

Doxepin inhibits GPVI-dependent platelet Ca2+ signaling and collagen-dependent thrombus formation
In conclusion, doxepin is a powerful inhibitor of GPVI-dependent platelet Ca2+ signaling, platelet activation, and thrombus formation. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - June 7, 2017 Category: Cytology Authors: Geue, S., Walker-Allgaier, B., Eissler, D., Tegtmeyer, R., Schaub, M., Lang, F., Gawaz, M., Borst, O., Münzer, P. Tags: RESEARCH ARTICLE Source Type: research