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Intracellular extracellular

Hoda Fathali, Johan Dunevall, Soodabeh Majdi, Ann-Sofie Cans
Amperometry recording of cells subjected to osmotic shock show that secretory cells respond to this physical stress by reducing the exocytosis activity and the amount of neurotransmitter released from vesicles in single exocytosis events. It has been suggested that the reduction in neurotransmitters expelled is due to alterations in membrane biophysical properties when cells shrink in response to osmotic stress and with assumptions made that secretory vesicles in the cell cytoplasm are not affected by extracellular osmotic stress...
February 19, 2018: Journal of Visualized Experiments: JoVE
Xiangpeng Hu, Hongwei Kan, Alex Boye, Yufeng Jiang, Chao Wu, Yan Yang
The transforming growth factor (TGF)-β/Smad signaling pathway is involved in hepatocellular carcinoma development. Smad2 and Smad3 are phosphorylated following TGF-β1 stimulation and subsequently oligomerize with Smad4 to form the Smad2/3/4 complex, which translocates into the nucleus and regulates target genes, including plasminogen activator inhibitor type 1 (PAI1). Importin (Imp)7 and Imp8 are responsible for transporting phosphorylated (p)Smad2/3 and Smad4 into the nucleus. In our previous study, it was demonstrated that mitogen-activated protein kinase (MAPK) inhibitors, including inhibitors of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 could inhibit the transcription of PAI1, but ERK inhibitor had no significant effect on the phosphorylation of Smad2/3, and the formation of Smad2/3/4 complexes, which was different from the effect of JNK or p38 inhibitor...
April 2018: Oncology Letters
Miyuki Kuno
A proton is a ubiquitous signaling ion. Many transmembrane H+ transport pathways either maintain pH homeostasis or generate acidic compartments. The osteoclast is a bone-resorbing cell, which degrades bone tissues by secreting protons and lysosomal enzymes into the resorption pit. The plasma membrane facing bone tissue (ruffled border), generated partly by fusion of lysosomes, may mimic H+ flux mechanisms regulating acidic vesicles. We identified three electrogenic H+ -fluxes in osteoclast plasma membranes-a vacuolar H+ -ATPase (V-ATPase), a voltage-gated proton channel (Hv channel) and an acid-inducible H+ -leak-whose electrophysiological profiles and regulation mechanisms differed...
March 17, 2018: Pflügers Archiv: European Journal of Physiology
Ruru Guo, Yang Tu, Shaowei Xie, Xue Song Liu, Yang Song, Suli Wang, Xiaoxiang Chen, Liangjing Lu
BACKGROUND/AIMS: Neutrophil extracellular traps (NETs) are known to play an important role in systemic lupus erythematosus (SLE) by triggering innate and adaptive immune responses. The molecular mechanisms responsible for their formation in SLE are still unclear. In this study, we aim to characterize the role of the receptor-interacting protein kinase-1 (RIPK1), a homologous serine/threonine kinase previously implicated in the regulation of necroptosis and tissue injury, in decreasing neutrophil death and formation of NETs, and to investigate the clinical implications of RIPK1 in SLE...
March 13, 2018: Cellular Physiology and Biochemistry
Xin Li, James A Imlay
Escherichia coli is a model organism that has been exploited to reveal key details of hydrogen peroxide stress: the biomolecules that H2 O2 most rapidly damages and the defensive tactics that organisms use to fend it off. Much less clear is the amount of exogenous H2 O2 that is sufficient to injure the bacterium and/or to trigger its stress response. To fill this gap, we need to study the behavior of cells when they are exposed to defined amounts of H2 O2 on an hours-long time scale. Such experiments are difficult because bacteria rapidly consume H2 O2 that is added to test cultures...
March 14, 2018: Free Radical Biology & Medicine
Chittabrata Mal, Md Aftabuddin, Sudip Kundu
BACKGROUND: Growing evidences suggest that microRNAs (miRNAs) can efficiently regulate gene expression at intracellular and extracellular levels. It has been previously reported that plant/food-derived miRNAs are highly enriched in human serum or serum from phytophagous animals, and they are responsible for regulating mammalian gene expression. Thus, miRNAs could function as active signaling molecules, which carry information across distinct species or even kingdoms. However, the mode of miRNA shuttling among various organisms is still a mystery to unravel...
March 16, 2018: Interdisciplinary Sciences, Computational Life Sciences
Safa Ben Mimouna, Sana Boughammoura, Marouane Chemek, Zohra Haouas, Mohamed Banni, Imed Messaoudi
This study was carried out to investigate the effects of maternal Cd and/or Zn exposure on some parameters of Zn metabolism in fetal brain of Wistar rats. Thus, female controls and other exposed by the oral route during the gestation period to Cd (50 mg CdCl2 /L) and/or Zn (ZnCl2 60 mg/L) were used. The male fetuses at age 20 days of gestation (GD20) were sacrificed and their brains were taken for histological, chemical and molecular analysis. Zn depletion was observed in the brains of fetuses issued from mothers exposed to Cd...
March 13, 2018: Chemico-biological Interactions
Eva Jover, Ana Silvente, Francisco Marín, José Martínez-González, Mar Orriols, Carlos M Martinez, Carmen María Puche, Mariano Valdés, Cristina Rodriguez, Diana Hernández-Romero
Vascular smooth muscle cells (VSMCs) transdifferentiate into osteoblast-like cells during vascular calcification, inducing active remodeling and calcification of the extracellular matrix (ECM). Intracellular and extracellular enzymes, such as lysyl hydroxylase 1 (PLOD1) and lysyl oxidase (LOX), contribute to ECM maturation and stabilization. We assessed the contribution of these enzymes to hyperphosphatemia (HPM)-induced calcification. Human and murine VSMCs were differentiated into functional osteoblast-like cells by HPM conditioning...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Meng Liu, Shiyang Shen, Di Wen, Mengru Li, Teng Li, Xiaojie Chen, Zhen Gu, Ran Mo
Protein therapeutics hold increasing interest with promise of revolutionizing the cancer treatment by virtue of potent specific activity and reduced adverse effect. Nonetheless, the therapeutic efficacy of anticancer proteins is highly compromised by multiple successive physiological barriers to protein delivery. Concurrent elimination of bulk tumor cells and highly-tumorigenic cancer stem-like cells (CSCs) has been evidenced as a promising strategy to improve cancer therapy. Here we show that a hierarchically-assembled nanocomposite can self-adaptively transform its particulate property in response to endogenous tumor-associated signals to overcome the sequential barriers and achieve enhanced antitumor efficacy by killing CSCs and bulk tumor cells synchronously...
March 16, 2018: Nano Letters
Jianjun Chang, Yan Ding, Zhiyu Zhou, Hong-Guang Nie, Hong-Long Ji
Transepithelial fluid and salt re-absorption in epithelial tissues play an important role in fluid and salt homeostasis. In absorptive epithelium, fluid and salt flux is controlled by machinery mainly composed of epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), Na⁺/H⁺ exchanger (NHE), aquaporin, and sodium potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). Dysregulation of fluid and salt transport across epithelium contributes to the pathogenesis of many diseases, such as pulmonary edema and cystic fibrosis...
March 16, 2018: International Journal of Molecular Sciences
Kyle I Mentkowski, Jonathan D Snitzer, Sarah Rusnak, Jennifer K Lang
Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease...
March 15, 2018: AAPS Journal
Huan Gao, Yue Zhang, Lei Dong, Xiao-Yu Qu, Li-Na Tao, Yue-Ming Zhang, Jing-Hui Zhai, Yan-Qing Song
To investigate the effects of triptolide (TPI) on proliferation, autophagy and death in human breast cancer MCF-7 cells, and to elucidate the associated molecular mechanisms, intracellular alterations were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The results of the MTT assay revealed that TPI significantly reduced the MCF-7 cell survival rate when the concentration was >10 nmol/l. TPI activated a caspase cascade reaction by regulating Bcl-2-associated X protein (Bax), caspase-3 and B-cell lymphoma 2 expression, and promoted programmed cell death via the mitochondrial pathway...
April 2018: Experimental and Therapeutic Medicine
Anas H Abu-Humaidan, Malin Elvén, Andreas Sonesson, Peter Garred, Ole E Sørensen
The complement system is an ancient part of the innate immune system important for both tissue homeostasis and host defense. However, bacteria like Staphylococcus aureus (SA) possess elaborative mechanisms for evading both the complement system and other parts of the immune system. One of these evasive mechanisms-important in causing chronic and therapy resistant infections-is the intracellular persistence in non-immune cells. The objective of our study was to investigate whether persistent intracellular SA infection of epidermal keratinocytes resulted in complement activation...
2018: Frontiers in Immunology
A Covarrubias-Pinto, A I Acuña, G Boncompain, E Pápic, P V Burgos, F Perez, M A Castro
Ascorbic acid (Asc) is an antioxidant molecule essential for physiological functions. The concentration of extracellular Asc increases during synaptic transmission and renal reabsorption. These phenomena induce an increase of the Sodium-dependent-Vitamin-C-transporter 2 (SVCT2) at plasma membrane (PM) localization, as we previously demonstrated in neuronal and non-neuronal cells. Hence, the aim of this study was to evaluate intracellular SVCT2 trafficking kinetics in response to Asc. We observed two peaks of SVCT2 localization and function at the PM (at 5-10min, "acute response", and 30-60min, "post-acute response") when cells were incubated with Asc...
March 12, 2018: Free Radical Biology & Medicine
Stella Arelaki, Athanasios Arampatzioglou, Konstantinos Kambas, Efthimios Sivridis, Alexandra Giatromanolaki, Konstantinos Ritis
Inflammation is a hallmark of colorectal cancer (CRC). Neutrophils are well-known mediators in tumor biology but their role in solid tumors, including CRC, was redefined by neutrophil extracellular traps (NETs). Given that it was recently demonstrated that platelet-derived polyP primes neutrophils to release NETs, we examined surgical specimens from CRC to investigate the presence of polyP, as a possible NET inducer. Biopsies with adenomas, hyperplastic polyps, inflammatory bowel disease and healthy colon tissues were used as controls...
2018: PloS One
Anish Sharda, Bruce Furie
The protein disulfide isomerase (PDI) family of thiol isomerases are intracellular enzymes known to catalyze the oxidation, reduction and isomerization of disulfide bonds during protein synthesis in the endoplasmic reticulum. PDI and related members of the thiol isomerase family are known to localize extracellularly where they possess various functions. Among these, the role of PDI in the initiation of thrombus formation is best characterized. PDI is secreted within seconds from activated platelets and endothelial cells at the site of vascular injury and accumulates in the developing platelet-fibrin thrombus...
March 15, 2018: Expert Review of Hematology
Evan Tan, Harry H Asada, Ruowen Ge
NOTCH signalling is an evolutionarily conserved juxtacrine signalling pathway that is essential in development. Jagged1 (JAG1) and Delta-like ligand 4 (DLL4) are transmembrane NOTCH ligands that regulate angiogenesis by controlling endothelial cell (EC) differentiation, vascular development and maturation. In addition, DLL4 could bypass its canonical cell-cell contact-dependent signalling to influence NOTCH signalling and angiogenesis at a distance when it is packaged into extracellular vesicles (EVs). However, it is not clear whether JAG1 could also be packaged into EVs to influence NOTCH signalling and angiogenesis...
March 14, 2018: Angiogenesis
Josette M Northcott, Ivory S Dean, Janna K Mouw, Valerie M Weaver
The tumor microenvironment is a dynamic landscape in which the physical and mechanical properties evolve dramatically throughout cancer progression. These changes are driven by enhanced tumor cell contractility and expansion of the growing tumor mass, as well as through alterations to the material properties of the surrounding extracellular matrix (ECM). Consequently, tumor cells are exposed to a number of different mechanical inputs including cell-cell and cell-ECM tension, compression stress, interstitial fluid pressure and shear stress...
2018: Frontiers in Cell and Developmental Biology
Marta Stolarczyk, Bob J Scholte
Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share molecular mechanisms that cause the pathological symptoms they have in common. Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis plays a role in the development of chronic lung disease in both CF and COPD. The ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) forms a functional unit with the EGF receptor (EGFR), in a feedback loop interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands such as amphiregulin (AREG), and proinflammatory mediators such as the interleukin 6 coreceptor (IL-6R)...
2018: Mediators of Inflammation
Tatsuya Yamada, Makoto Nishiyama, Shigeyuki Oba, Henri Claver Jimbo, Kazushi Ikeda, Shin Ishii, Kyonsoo Hong, Yuichi Sakumura
Biological cells express intracellular biomolecular information to the extracellular environment as various physical responses. We show a novel computational approach to estimate intracellular biomolecular pathways from growth cone electrophysiological responses. Previously, it was shown that cGMP signaling regulates membrane potential (MP) shifts that control the growth cone turning direction during neuronal development. We present here an integrated deterministic mathematical model and Bayesian reversed-engineering framework that enables estimation of the molecular signaling pathway from electrical recordings and considers both the system uncertainty and cell-to-cell variability...
March 14, 2018: Scientific Reports
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