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American Journal of Physiology. Cell Physiology

Su Dong, Jia Liu, Lian Li, Heather Wang, Haichun Ma, Yutong Zhao, Jing Zhao
Opioids are widely used for relieving clinical acute or chronic pain. The biological effects of opioids are through activating the μ-opioid receptors 1 (MOR1). Most studies have focused on the consequences of agonist-induced MOR1 phosphorylation, ubiquitination, and internalization. Agonist-mediated MOR1 degradation, which is crucial for receptor stability and responsiveness, has not been well studied. The HECT ubiquitin E3 ligase Smurf2 has been shown to regulate MOR1 ubiquitination and internalization, however, its role in MOR1 degradation has not been studied...
February 13, 2019: American Journal of Physiology. Cell Physiology
Nadia Bouhamdani, Dominique Comeau, Kevin Cormier, Sandra Turcotte
Autophagy is a highly conserved, homeostatic process by which cytosolic components reach lysosomes for degradation. The roles that play different autophagic processes in cancer are complex and remain cancer-type and -stage dependent. Renal cell carcinoma (RCC) is the most common subtype of kidney cancer and is characterized by the inactivation of the VHL tumor suppressor. Our previous study identified a small compound, STF-62247 as an autophagy-modulating molecule causing selective cytotoxicity for VHL-inactivated cells...
February 13, 2019: American Journal of Physiology. Cell Physiology
Ashley N Haddock, Sydney A Labuzan, Amy E Haynes, Caleb S Hayes, Karina M Kakareka, David S Waddell
Skeletal muscle atrophy results from disparate physiological conditions, including denervation, corticosteroid treatment, and aging. The purpose of this study was to describe and characterize the function of dual-specificity phosphatase 4 (Dusp4) in skeletal muscle after it was found to be induced in response to neurogenic atrophy. qPCR and Western blot analysis revealed that Dusp4 is expressed during myoblast proliferation, but rapidly disappears as muscle cells differentiate. The Dusp4 regulatory region was cloned and found to contain a conserved E-box element that negatively regulates Dusp4 reporter gene activity in response to myogenic regulatory factor expression...
February 13, 2019: American Journal of Physiology. Cell Physiology
Stephane M Adaniya, Jin O-Uchi, Michael W Cypress, Yoichiro Kusakari, Bong Sook Jhun
Mitochondrial fragmentation frequently occurs in chronic pathological conditions as seen in various human diseases. In fact, abnormal mitochondrial morphology and mitochondrial dysfunction are hallmarks of heart failure (HF) in both human patients and HF animal models. A link between mitochondrial fragmentation and cardiac pathologies has widely been proposed, but the physiological relevance of mitochondrial fission/fusion in the heart is still unclear. Recent studies have increasingly shown that post-translational modifications (PTMs) of fission/fusion proteins are capable of directly modulating the stability, localization, and/or activity of these proteins...
February 13, 2019: American Journal of Physiology. Cell Physiology
Lauren Parker Huff, Daniel Seicho Kikuchi, Elizabeth Faidley, Steven J Forrester, Michelle Z Tsai, Bernard Lassègue, Kathy K Griendling
Polymerase delta interacting protein 2 (Poldip2) controls a wide variety of cellular functions and vascular pathologies. To mediate these effects, Poldip2 interacts with numerous proteins and generates reactive oxygen species via the enzyme NADPH oxidase 4 (Nox4). We have previously shown that Poldip2 can activate the Rho family GTPase RhoA, another signaling node within the cell. In this study, we aimed to better understand how Poldip2 activates Rho family GTPases and the functions of the involved proteins in vascular smooth muscle cells (VSMCs)...
February 6, 2019: American Journal of Physiology. Cell Physiology
Shuang Peng, Shenbao Chen, Linda Li, Chun-Fang Tong, Ning Li, Shou-Qin Lü, Mian Long
L-selectin shedding induced by various cytokines is crucial in activating neutrophils (PMNs) in inflammatory cascade. While the real-time shedding in vivo lasts about 10 min after PMN activation, the impact of time-dependent shedding on binding kinetics of membrane-remaining L-selectins to its ligands is poorly understood at transient or steady state. Here we developed an in vitro L-selectin shedding dynamics approach, together with competitive assays of cell adhesion, and proposed a theoretical model for quantifying the impact of real-time shedding on the binding kinetics of membrane-remaining L-selectins to PSGL-1...
February 6, 2019: American Journal of Physiology. Cell Physiology
Yan Dong, Jun Wang, Kai-Xian Du, Tian-Ming Jia, Chang-Lian Zhu, Yan Zhang, Fa-Lin Xu
Accumulating evidence has highlighting the potential of microRNAs (miRs) as biomarkers in various human diseases. However, the roles of miRs in bacterial meningitis (BM), a severe infectious condition, still remain unclear. Thus, the present study aimed to investigate the effects of miR-135a on proliferation and apoptosis of astrocytes in BM. Neonatal rats were injected with streptococcus pneumoniae to establish the BM model. The expression of miR-135a and HIF-1α in the BM rat models were characterized, followed by determination of their interaction...
February 6, 2019: American Journal of Physiology. Cell Physiology
Tsubasa S Matsui, Shinji Deguchi
The phosphorylation state of myosin regulatory light chain (MRLC) is central to the regulation of contractility that in turn impacts cellular homeostasis and fate decisions. Rho-kinase (ROCK) and myosin light chain kinase (MLCK) are major kinases for MRLC documented to selectively regulate MRLC in a subcellular position-specific manner; specifically, MLCK in some nonmuscle cell types works in the cell periphery to promote migration, while ROCK does at the central region to sustain contractility. However, it remains unclear whether or not the spatially selective regulation of the MRLC kinases is universally present in other cell types including dedifferentiated vascular smooth muscle cells (SMCs)...
January 30, 2019: American Journal of Physiology. Cell Physiology
Yalan Xu, Lili Sui, Bintao Qiu, Xiuju Yin, Juntao Liu, Xiaohong Zhang
OBJECTIVES: The inadequate trophoblast invasion is associated with the development of preeclampsia (PE). Considering that annexin A4 (ANXA4) enhances tumor invasion, we aimed to explore the functional role of ANXA4 in trophoblast cells and to examine the underlying mechanism. METHODS: ANXA4 expression in PE placentas was analyzed using immunohistochemistry and Western blot. Cell proliferation, invasion, and apoptosis were determined using MTT assay, Transwell assay, and flow cytometry, respectively...
January 23, 2019: American Journal of Physiology. Cell Physiology
Li-Ping Jiang, Shelley R Wang, Hee Kyoung Chung, Saharsh Buddula, Jian-Ying Wang, Jaladanki N Rao
Both zipcode binding protein-1 (ZBP1) and phospholipase C-γ1 (PLC-γ1) are intimately involved in many aspects of early intestinal mucosal repair after acute injury, but the exact mechanisms that control their cellular abundances remain largely unknown. The present study shows that microRNA 222 (miR-222) interacts with the mRNAs encoding ZBP1 and PLC-γ1 and thus regulates ZBP1 and PLC-γ1 expression in intestinal epithelial cells (IECs). The biotinylated miR-222 specifically bound to the ZBP1 and PLC-γ1 mRNAs in IECs...
January 16, 2019: American Journal of Physiology. Cell Physiology
Amanda J Genders, Sheree D Martin, Sean L McGee, David J Bishop
Exercise stimulates mitochondrial biogenesis and increases mitochondrial respiratory function and content. However, during high-intensity exercise muscle pH can decrease below pH 6.8 with a concomitant increase in lactate concentration. This drop in muscle pH is associated with reduced exercise-induced mitochondrial biogenesis, whilst increased lactate may act as a signaling molecule to affect mitochondrial biogenesis. Therefore, in this study we wished to determine the impact of altering pH and lactate concentration in L6 myotubes on genes and proteins known to be involved in mitochondrial biogenesis...
January 16, 2019: American Journal of Physiology. Cell Physiology
Toshiaki Sawatani, Yukiko K Kaneko, Isao Doutsu, Ai Ogawa, Tomohisa Ishikawa
β-Cell swelling induces membrane depolarization, which has been suggested to be caused at least partly by the activation of cation channels. Here, we show the identification of the cation channels. In isolated mouse pancreatic β-cells, the exposure to 30% hypotonic solution elicited an increase in cytosolic Ca2+ concentration ([Ca2+ ]c ). The [Ca2+ ]c elevation was partially inhibited by ruthenium red, a blocker of several Ca2+ -permeable channels including transient receptor potential vanilloid receptors (TRPV), and by nicardipine, but not by the depletion of intracellular Ca2+ stores with thapsigargin and caffeine...
January 16, 2019: American Journal of Physiology. Cell Physiology
Peter K Lauf, Neelima Sharma, Norma C Adragna
During aging, and development of atherosclerosis and cardiovascular disease (CVD), aortic vascular smooth muscle cells (VSMCs) transition from healthy contractile to diseased synthetic phenotypes. K-Cl cotransport (KCC) maintains cell volume and ion homeostasis in growth and differentiation, and hence is important for VSMC proliferation and migration. Therefore, KCC activity may play a role in the contractile to synthetic VSMC phenotypic transition. Early, medium, and late synthetic passage VSMCs were tested for specific cytoskeletal protein expression...
January 16, 2019: American Journal of Physiology. Cell Physiology
David J Allison, Joshua P Nederveen, Tim Snijders, Kirsten E Bell, Dinesh Kumbhare, Stuart M Phillips, Gianni Parise, Jennifer Heisz
Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence Trp metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Although exercise training has been shown to improve skeletal muscle mass in older adults, whether this also translates into improvements in transcription factors and metabolites related to the kynurenine pathway has yet to be examined...
January 16, 2019: American Journal of Physiology. Cell Physiology
Zhen Zheng, Hairu Chen, Peilin Xie, Carol A Dickerson, Judy A C King, Mikhail F Alexeyev, Hee-Sup Shin, Songwei Wu
Pulmonary microvascular endothelial cells (PMVECs) display a rapid angioproliferative phenotype, essential for maintaining homeostasis in steady state and promoting vascular repair after injury. Although it has long been established that endothelial cytosolic Ca2+ ([Ca2+ ]i ) transients are required for proliferation and angiogenesis, mechanisms underlying such regulation and the transmembrane channels mediating the relevant [Ca2+ ]i transients remain incompletely understood. In the present study, the functional role of microvascular endothelial site-specific α1G T-type Ca2+ channel in angiogenesis was examined...
January 16, 2019: American Journal of Physiology. Cell Physiology
Marwa Mahmoud, Ian M Evans, Vedanta Mehta, Caroline Pellet-Many, Ketevan Paliashvili, Ian Zachary
Neuropilin 1 (NRP1) is important for neuronal and cardiovascular development due to its role in conveying class 3 semaphorin and vascular endothelial growth factor signalling, respectively. NRP1 is expressed in smooth muscle cells (SMCs) and mediates their migration and proliferation in cell culture, and is implicated in pathological SMC remodelling in vivo. To address the importance of Nrp1for SMC function during development, we generated conditional inducible Nrp1SMC-specific knockout mice. Induction of early postnatal SMC-specific Nrp1knockout led to pulmonary haemorrhage associated with defects in alveogenesis, and revealed a specific requirement for Nrp1in myofibroblast recruitment to the alveolar septae and PDGF-AA-induced migration in vitro...
January 16, 2019: American Journal of Physiology. Cell Physiology
Jutaro Fukumoto, Sahebgowda Sidramagowda Patil, Sudarshan Krishnamurthy, Smita Saji, Irene John, Venkata Ramireddy Narala, Helena Hernández-Cuervo, Matthew Alleyn, Mason T Breitzig, Lakshmi Galam, Ramani Soundararajan, Uddhav K Chaudhari, Barbara C Hansen, Richard F Lockey, Narasaiah Kolliputi
Aging is a key contributor for subclinical progression of late-onset lung diseases. Basal, club, and type II alveolar epithelial cells are lung epithelial progenitors whose capacities of differentiation are extensively studied. The timely transition of these cells in response to environmental changes helps maintain the intricate organization of lung structure. However, it remains unclear how aging affects their behavior. This paper demonstrates that the protein expression profiles of a type II AEC marker, prosurfactant protein C (pro-SPC), and a basal cell marker, p63, are altered in the lungs of 14-month-old versus 7-9-week-old mice...
January 16, 2019: American Journal of Physiology. Cell Physiology
Wei Dong, Fei Xie, Xuan-Ying Chen, Wei-Lin Huang, Yu-Zhen Zhang, Wen-Bo Luo, Jin Chen, Ming-Tuan Xie, Yu Liu, Xiao-Ping Peng
BACKGROUND: myocardial ischemia/reperfusion (I/R) is a common and lethal disease that threatens people's life worldwide. The underlying mechanisms are under intensive study and yet remain unclear. Here, we explored the function of miR-322/503 in myocardial I/R injury. METHODS: We used isolated rat perfused heart as an in vivo model and H9c2 cells subjected with the oxygen and glucose deprivation followed by reperfusion (OGD/R) as in vitro model to study myocardial I/R injury...
January 16, 2019: American Journal of Physiology. Cell Physiology
Haiming Liu, LaDora V Thompson
RATIONALE: Unilateral denervation is widely-used for studies investigating mechanisms of muscle atrophy. The "contralateral-innervated muscle" is a commonly used experimental control in denervation studies. So far, it is not clear whether denervation unilaterally alters the proteolytic system in the contralateral-innervated muscles. Therefore, the objectives of this rapid report include 1) to determine whether unilateral denervation has an effect on the proteolytic system in contralateral-innervated control muscles; and 2) to identify the changes in proteasome properties in denervated muscles post 7- and 14-day tibial nerve transection by using either the contralateral-innervated muscles or intact muscles from non-surgical mice as the experimental control...
January 9, 2019: American Journal of Physiology. Cell Physiology
Yun Li, Yue Zhang, Xiaoli Zhang, Xiaoyan Feng, Chenzhe Liu, Xiuneng Zhang, Zhusheng Quan, Jingting Yan, Jinxia Zhu
Dopamine regulates gastrointestinal mucosal barrier. Mucus plays important roles in protection of intestinal mucosa. Here, the regulatory effect of dopamine on rat colonic mucus secretion was investigated. RT-PCR, immunofluorescence, Periodic Acid-Schiff's reagent assay, Alcian Blue-Periodic Acid Schiff staining, and enzyme-linked immunosorbent assay were used to observe the expression of dopamine receptor and the direct effect of dopamine on the colonic mucus. Mice injected intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) destroying enteric DA neurons, rats microinjected with 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra damaging central dopaminergic neurons, and dopamine D5 receptor down-regulated transgenic mice were used to detect the effect of endogenous enteric dopamine or dopamine receptors on distal colonic mucus...
January 9, 2019: American Journal of Physiology. Cell Physiology
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