ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis
Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria play a critical role in growth factor-induced switch from a quiescent to an angiogenic phenotype in endothelial cells (ECs). However, how highly diffusible ROS produced from different sources can coordinate to stimulate VEGF signaling and drive the angiogenic process remains unknown. Using the cytosol- and mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging, here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min, w...
Source: AJP: Cell Physiology - June 7, 2017 Category: Cytology Authors: Kim, Y.-M., Kim, S.-J., Tatsunami, R., Yamamura, H., Fukai, T., Ushio-Fukai, M. Tags: RESEARCH ARTICLE Source Type: research
Biphasic adaptation to osmotic stress in the C. elegans germ line
Cells respond to environmental stress in multiple ways. In the germ line, heat shock and nutritive stress trigger the assembly of large ribonucleoprotein (RNP) granules via liquid-liquid phase separation (LLPS). The RNP granules are hypothesized to maintain the quality of oocytes during stress. The goal of this study was to investigate the cellular response to glucose in the germ line and determine if it is an osmotic stress response. We found that exposure to 500 mM glucose induces the assembly of RNP granules in the germ line within 1 h. Interestingly, the RNP granules are maintained for up to 3 h; however, they dissocia...
Source: AJP: Cell Physiology - June 7, 2017 Category: Cytology Authors: Davis, M., Montalbano, A., Wood, M. P., Schisa, J. A. Tags: RESEARCH ARTICLE Source Type: research
Hemoglobin inhibits albumin uptake by proximal tubule cells: implications for sickle cell disease
Proximal tubule (PT) dysfunction, including tubular proteinuria, is a significant complication in young sickle cell disease (SCD) that can eventually lead to chronic kidney disease. Hemoglobin (Hb) dimers released from red blood cells upon hemolysis are filtered into the kidney and internalized by megalin/cubilin receptors into PT cells. The PT is especially sensitive to heme toxicity, and tubular dysfunction in SCD is thought to result from prolonged exposure to filtered Hb. Here we show that concentrations of Hb predicted to enter the tubule lumen during hemolytic crisis competitively inhibit the uptake of another megali...
Source: AJP: Cell Physiology - June 7, 2017 Category: Cytology Authors: Eshbach, M. L., Kaur, A., Rbaibi, Y., Tejero, J., Weisz, O. A. Tags: RESEARCH ARTICLE Source Type: research
Ulk1-mediated autophagy plays an essential role in mitochondrial remodeling and functional regeneration of skeletal muscle
Autophagy is a conserved cellular process for degrading aggregate proteins and dysfunctional organelle. It is still debatable if autophagy and mitophagy (a specific process of autophagy of mitochondria) play important roles in myogenic differentiation and functional regeneration of skeletal muscle. We tested the hypothesis that autophagy is critical for functional regeneration of skeletal muscle. We first observed time-dependent increases (3- to 6-fold) of autophagy-related proteins (Atgs), including Ulk1, Beclin1, and LC3, along with reduced p62 expression during C2C12 differentiation, suggesting increased autophagy capac...
Source: AJP: Cell Physiology - June 7, 2017 Category: Cytology Authors: Call, J. A., Wilson, R. J., Laker, R. C., Zhang, M., Kundu, M., Yan, Z. Tags: RESEARCH ARTICLE Source Type: research
Identification of the fatty acid activation site on human ClC-2
Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl– channel activators. Molecular and cellular mechanisms underlying this activation were examined. Role of a four-amino acid PKA activation site, RGET691, of hClC-2 was investigated using wild-type (WT) and mutant (AGET, RGEA, and AGAA) hClC-2 expressed in 293EBNA cells as well as involvement of PKA, intracellular cAMP concentration ([cAMP]i), EP2, or EP4 receptor agonist activity. All fatty acids [lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid, and elaidic acid] caused significant rightward shifts in concentration-d...
Source: AJP: Cell Physiology - June 7, 2017 Category: Cytology Authors: Cuppoletti, J., Tewari, K. P., Chakrabarti, J., Malinowska, D. H. Tags: RESEARCH ARTICLE Source Type: research
Neurotrophin 3 upregulates proliferation and collagen production in human aortic valve interstitial cells: a potential role in aortic valve sclerosis
Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3). In the present study, we tested the hypothesis that NT3 is a profibrogenic factor to human AVICs. AVICs isolated ...
Source: AJP: Cell Physiology - June 1, 2017 Category: Cytology Authors: Yao, Q., Song, R., Ao, L., Cleveland, J. C., Fullerton, D. A., Meng, X. Tags: RESEARCH ARTICLE Source Type: research
Multiple AMPK activators inhibit L-carnitine uptake in C2C12 skeletal muscle myotubes
Mutations in the gene that encodes the principal l-carnitine transporter, OCTN2, can lead to a reduced intracellular l-carnitine pool and the disease Primary Carnitine Deficiency. l-Carnitine supplementation is used therapeutically to increase intracellular l-carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake, we hypothesized that AMPK-activating compounds and insulin would increase l-carnitine uptake in C2C12 myotubes. The cells express all three OCTN transporters at the mRNA level, and immunohistochemistry confirmed expression at the protein level. Contrary to our hypothesis, despite significant ...
Source: AJP: Cell Physiology - June 1, 2017 Category: Cytology Authors: Shaw, A., Jeromson, S., Watterson, K. R., Pediani, J. D., Gallagher, I. J., Whalley, T., Dreczkowski, G., Brooks, N., Galloway, S. D., Hamilton, D. L. Tags: RESEARCH ARTICLE Source Type: research
Rethinking the regulation of L-carnitine transport in skeletal muscle cells. Focus on "Multiple AMPK activators inhibit L-carnitine uptake in C2C12 skeletal muscle myotubes"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - June 1, 2017 Category: Cytology Authors: Xu, D., You, G. Tags: EDITORIAL FOCUS Source Type: research
Transport across the choroid plexus epithelium
The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the cho...
Source: AJP: Cell Physiology - June 1, 2017 Category: Cytology Authors: Praetorius, J., Damkier, H. H. Tags: REVIEW Source Type: research
miR-375 negatively regulates the synthesis and secretion of catecholamines by targeting Sp1 in rat adrenal medulla
The adrenal gland is an important endocrine gland in balancing homeostasis and the response to stress by synthesizing and secreting catecholamines (CATs), and it has been confirmed that microRNA-375 (miR-375) is highly expressed in adrenal medulla. However, up to now there are few reports about the functions and related mechanisms in adrenal medulla. The present study was thus designed to study the roles and related mechanisms in rat adrenal medulla. Our results showed that miR-375 was specifically expressed in rat adrenal medulla chromaffin cells, and its expression was downregulated when rats were exposed to stress. The ...
Source: AJP: Cell Physiology - May 11, 2017 Category: Cytology Authors: Gai, Y., Zhang, J., Wei, C., Cao, W., Cui, Y., Cui, S. Tags: RESEARCH ARTICLE Source Type: research
H2O2 augments cytosolic calcium in nucleus tractus solitarii neurons via multiple voltage-gated calcium channels
Reactive oxygen species (ROS) play a profound role in cardiorespiratory function under normal physiological conditions and disease states. ROS can influence neuronal activity by altering various ion channels and transporters. Within the nucleus tractus solitarii (nTS), a vital brainstem area for cardiorespiratory control, hydrogen peroxide (H2O2) induces sustained hyperexcitability following an initial depression of neuronal activity. The mechanism(s) associated with the delayed hyperexcitability are unknown. Here we evaluate the effect(s) of H2O2 on cytosolic Ca2+ (via fura-2 imaging) and voltage-dependent calcium current...
Source: AJP: Cell Physiology - May 11, 2017 Category: Cytology Authors: Ostrowski, T. D., Dantzler, H. A., Polo-Parada, L., Kline, D. D. Tags: RESEARCH ARTICLE Source Type: research
{alpha}7{beta}1 Integrin regulation of gene transcription in skeletal muscle following an acute bout of eccentric exercise
The α7β1 integrin is concentrated at the costameres of skeletal muscle and provides a critical link between the actin cytoskeleton and laminin in the basement membrane. We previously demonstrated that expression of the α7BX2 integrin subunit (MCK:α7BX2) preserves muscle integrity and enhances myofiber cross-sectional area following eccentric exercise. The purpose of this study was to utilize gene expression profiling to reveal potential mechanisms by which the α7BX2-integrin contributes to improvements in muscle growth after exercise. A microarray analysis was performed using RNA extracted from...
Source: AJP: Cell Physiology - May 11, 2017 Category: Cytology Authors: Mahmassani, Z. S., Son, K., Pincu, Y., Munroe, M., Drnevich, J., Chen, J., Boppart, M. D. Tags: RESEARCH ARTICLE Source Type: research
Membrane lipid rafts are disturbed in the response of rat skeletal muscle to short-term disuse
Marked loss of skeletal muscle mass occurs under various conditions of disuse, but the molecular and cellular mechanisms leading to atrophy are not completely understood. We investigate early molecular events that might play a role in skeletal muscle remodeling during mechanical unloading (disuse). The effects of acute (6–12 h) hindlimb suspension on the soleus muscles from adult rats were examined. The integrity of plasma membrane lipid rafts was tested utilizing cholera toxin B subunit or fluorescent sterols. In addition, resting intracellular Ca2+ level was analyzed. Acute disuse disturbed the plasma membrane lipi...
Source: AJP: Cell Physiology - May 11, 2017 Category: Cytology Authors: Petrov, A. M., Kravtsova, V. V., Matchkov, V. V., Vasiliev, A. N., Zefirov, A. L., Chibalin, A. V., Heiny, J. A., Krivoi, I. I. Tags: RESEARCH ARTICLE Source Type: research
Is it time to reinvent basic cell culture medium?
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - May 3, 2017 Category: Cytology Authors: McKee, T. J., Komarova, S. V. Tags: VIEWPOINT Source Type: research
Distinct physiological effects of {beta}1- and {beta}2-adrenoceptors in mouse ventricular myocytes: insights from a compartmentalized mathematical model
The β1- and β2-adrenergic signaling systems play different roles in the functioning of cardiac cells. Experimental data show that the activation of the β1-adrenergic signaling system produces significant inotropic, lusitropic, and chronotropic effects in the heart, whereas the effects of the β2-adrenergic signaling system is less apparent. In this paper, a comprehensive compartmentalized experimentally based mathematical model of the combined β1- and β2-adrenergic signaling systems in mouse ventricular myocytes is developed to simulate the experimental findings and make testable predictions of...
Source: AJP: Cell Physiology - May 3, 2017 Category: Cytology Authors: Rozier, K., Bondarenko, V. E. Tags: ARTICLES Source Type: research
