Extracellular Space

Publication Title: 
Neuropharmacology

We studied the effects of pentobarbital and antagonists of glutamate, gamma-aminobutyrate (GABA), and glycine receptors on extracellular activity in ventrobasal thalamic slices. Pentobarbital at sedative-hypnotic concentration (20 microM) reversibly induced 1-15 Hz oscillations. Sustained oscillations required electrical stimulation of internal capsule, but not elevated temperature or low [Mg2+]. Anesthetic concentration (200 microM) of pentobarbital evoked only transient oscillations. Kynurenate-sensitive glutamate receptors were essential for oscillations.

Author(s): 
Ran, I.
Mathers, D. A.
Puil, E.
Publication Title: 
Arzneimittel-Forschung

Two drugs composed of several different plant extracts are in use in Ayurvedic medicine for the treatment of asthma and arthritis, respectively. There is increasing evidence that reactive oxygen species (ROS) arising from several enzymatic reactions are mediators of inflammatory events such as the above mentioned. Plant extracts have the potential for scavenging such reactive oxygen species, dependent on the individual test system.

Author(s): 
Janisch, Kerstin M.
Milde, Jens
Elstner, Erich F.
Publication Title: 
Brain Research

Acidification, which occurs in some pathological conditions, such as ischemia and hypoxia often induces neurotoxicity. The activation of acid-sensing ion channels (ASICs), which are highly permeable to calcium, has been considered the main target responsible for calcium overload in ischemic/hypoxic brain. However, the influence of extracellular proton on GABAergic synaptic transmission is not well understood.

Author(s): 
Zhou, Chunyi
Xiao, Cheng
Deng, Chunyu
Hong Ye, Jiang
Publication Title: 
British Journal of Pharmacology

The intensity and duration of host responses are determined by protective mechanisms that control tissue injury by dampening down inflammation. Adenosine generation and consequent effects, mediated via A2A adenosine receptors (A2AR) on effector cells, play a critical role in the pathophysiological modulation of these responses in vivo. Adenosine is both released by hypoxic cells/tissues and is also generated from extracellular nucleotides by ecto-enzymes e.g. CD39 (ENTPD1) and CD73 that are expressed by the vasculature and immune cells, in particular by T regulatory cell.

Author(s): 
Sitkovsky, M.
Lukashev, D.
Deaglio, S.
Dwyer, K.
Robson, S. C.
Ohta, A.
Publication Title: 
British Journal of Pharmacology

BACKGROUND AND PURPOSE: The increased levels of extracellular adenosine in inflamed tissues down-regulate activated immune cells via the A(2A) adenosine receptor. This A(2A) adenosine receptor-mediated immunosuppression is a disqualifying obstacle in cancer immunotherapy as it protects cancerous tissues from adoptively transferred anti-tumour T cells. The aim of this study was to test whether the negative selection of T cells will produce T cells that are resistant to inhibition by extracellular adenosine.

Author(s): 
Ohta, Akio
Kjaergaard, J.
Sharma, S.
Mohsin, M.
Goel, N.
Madasu, M.
Fradkov, E.
Ohta, Akiko
Sitkovsky, M.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Immunosuppressive signaling via the A2A adenosine receptor (A2AR) provokes a mechanism that protects inflamed tissues from excessive damage by immune cells. This mechanism is desirable not only for preventing uncontrolled tissue destruction by overactive immune responses, but also for protecting tumor tissues from antitumor immune responses. In aforementioned circumstances, T cell priming may occur in an environment containing high concentrations of extracellular adenosine.

Author(s): 
Ohta, Akio
Ohta, Akiko
Madasu, Manasa
Kini, Radhika
Subramanian, Meenakshi
Goel, Nipun
Sitkovsky, Michail
Publication Title: 
Expert Opinion on Drug Metabolism & Toxicology

IMPORTANCE OF THE FIELD: Liver is the major body reservoir for enzymes involved in the metabolism of endogenous and xenobiotic compounds. Recently, it has been shown that hepatocytes release exosome-like vesicles to the extracellular medium, and the proteomic characterization of these hepatocyte-secreted exosomes has revealed the presence of several of these enzymes on them.

Author(s): 
Conde-Vancells, Javier
Gonzalez, Esperanza
Lu, Shelly C.
Mato, José M.
Falcon-Perez, Juan M.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione, which plays an important role in the bactericidal function of phagocytes. Because Gsr has been implicated in the oxidative burst in human neutrophils and is abundantly expressed in the lymphoid system, we hypothesized that Gsr-deficient mice would exhibit marked defects during the immune response against bacterial challenge.

Author(s): 
Yan, Jing
Meng, Xiaomei
Wancket, Lyn M.
Lintner, Katherine
Nelin, Leif D.
Chen, Bernadette
Francis, Kevin P.
Smith, Charles V.
Rogers, Lynette K.
Liu, Yusen
Publication Title: 
Bioscience, Biotechnology, and Biochemistry

Tremella mesenterica (TM) is a common food and folk medicine widely used in several Asian countries as a tonic for the lungs. In the present study, we compared the effects of extracellular polysaccharides (EPS), intracellular polysaccharides (IPS), and ethanol extract (EE) of Tremella mesenterica on the induction of apoptosis into human lung carcinoma A549 epithelial cells. The EE, but not the EPS or the IPS, almost completely inhibited the growth of A549 cells.

Author(s): 
Chen, Nan-Yin
Lai, Hsi-Huai
Hsu, Tai-Hao
Lin, Fang-Yi
Chen, Jian-Zhi
Lo, Hui-Chen
Publication Title: 
PloS One

Aging in organisms as diverse as yeast, nematodes, and mammals is delayed by caloric restriction, an effect mediated by the nutrient sensing TOR, RAS/cAMP, and AKT/Sch9 pathways. The transcription factor Gis1 functions downstream of these pathways in extending the lifespan of nutrient restricted yeast cells, but the mechanisms involved are still poorly understood. We have used gene expression microarrays to study the targets of Gis1 and the related protein Rph1 in different growth phases.

Author(s): 
Orzechowski Westholm, Jakub
Tronnersjö, Susanna
Nordberg, Niklas
Olsson, Ida
Komorowski, Jan
Ronne, Hans
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