The concentrative nucleoside transporter family (SLC28): new roles beyond salvage?

2005 ◽  
Vol 33 (1) ◽  
pp. 216-219 ◽  
Author(s):  
I. Aymerich ◽  
S. Duflot ◽  
S. Fernández-Veledo ◽  
E. Guillén-Gómez ◽  
I. Huber-Ruano ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Cell Physiology ◽  
Nucleoside Transporter ◽  
Cycle Progression ◽  
Suitable Candidate ◽  
Concentrative Nucleoside Transporter ◽  
Transporter Family ◽  
Nucleoside Salvage ◽  
Parenchymal Cells ◽  
Regulatory Properties

The concentrative nucleoside transporter (CNT) family (SLC28) has three members: SLC28A1 (CNT1), SLC28A2 (CNT2) and SLC28A3 (CNT3). The CNT1 and CNT2 transporters are co-expressed in liver parenchymal cells and macrophages, two suitable models in which to study cell cycle progression. Despite initial observations suggesting that these transporter proteins might contribute to nucleoside salvage during proliferation, their subcellular localization and regulatory properties suggest alternative roles in cell physiology. In particular, CNT2 is a suitable candidate for modulation of purinergic responses, since it is under the control of the adenosine 1 receptor. Increasing evidence also suggests a role for CNT2 in energy metabolism, since its activation relies on the opening of ATP-sensitive K+ channels. Animal and cell models genetically modified to alter nucleoside transporter expression levels may help to elucidate the particular roles of CNT proteins in cell physiology.

scholarly journals Dilazep, a nucleoside transporter inhibitor, modulates cell cycle progression and DNA synthesis in rat mesangial cells in vitro

2000 ◽  
Vol 33 (1) ◽  
pp. 19-28 ◽  
Author(s):  
T. Sakumura ◽  
Z. Fujii ◽  
S. Umemoto ◽  
T. Murakami & ◽  
Y. Kawata ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
Mesangial Cells ◽  
Nucleoside Transporter ◽  
Cycle Progression

scholarly journals In silico APC/C substrate discovery reveals cell cycle degradation of chromatin regulators including UHRF1

2020 ◽  
Author(s):  
Jennifer L. Kernan ◽  
Raquel C. Martinez-Chacin ◽  
Xianxi Wang ◽  
Rochelle L. Tiedemann ◽  
Thomas Bonacci ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
In Silico ◽  
Cell Cycle Progression ◽  
Vital Role ◽  
Regulatory Proteins ◽  
Phase Cell ◽  
Cell Physiology ◽  
Cycle Progression ◽  
Chromatin Regulator

AbstractThe Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase and critical regulator of cell cycle progression. Despite its vital role, it has remained challenging to globally map APC/C substrates. By combining orthogonal features of known substrates, we predicted APC/C substrates in silico. This analysis identified many known substrates and suggested numerous candidates. Unexpectedly, chromatin regulatory proteins are enriched among putative substrates and we show that several chromatin proteins bind APC/C, oscillate during the cell cycle and are degraded following APC/C activation, consistent with being direct APC/C substrates. Additional analysis revealed detailed mechanisms of ubiquitylation for UHRF1, a key chromatin regulator involved in histone ubiquitylation and DNA methylation maintenance. Disrupting UHRF1 degradation at mitotic exit accelerates G1-phase cell cycle progression and perturbs global DNA methylation patterning in the genome. We conclude that APC/C coordinates crosstalk between cell cycle and chromatin regulatory proteins. This has potential consequences in normal cell physiology, where the chromatin environment changes depending on proliferative state, as well as in disease.

scholarly journals Implication of Voltage-Gated Potassium Channels in Neoplastic Cell Proliferation

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 287 ◽  
Author(s):  
Clara Serrano-Novillo ◽  
Jesusa Capera ◽  
Magalí Colomer-Molera ◽  
Enric Condom ◽  
Joan Ferreres ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Potassium Channels ◽  
Cell Cycle Progression ◽  
Cell Function ◽  
Tumor Regression ◽  
Resting Potential ◽  
Volume Control ◽  
Cell Physiology ◽  
Cycle Progression ◽  
Voltage Gated

Voltage-gated potassium channels (Kv) are the largest group of ion channels. Kv are involved in controlling the resting potential and action potential duration in the heart and brain. Additionally, these proteins participate in cell cycle progression as well as in several other important features in mammalian cell physiology, such as activation, differentiation, apoptosis, and cell volume control. Therefore, Kv remarkably participate in the cell function by balancing responses. The implication of Kv in physiological and pathophysiological cell growth is the subject of study, as Kv are proposed as therapeutic targets for tumor regression. Though it is widely accepted that Kv channels control proliferation by allowing cell cycle progression, their role is controversial. Kv expression is altered in many cancers, and their participation, as well as their use as tumor markers, is worthy of effort. There is an ever-growing list of Kv that remodel during tumorigenesis. This review focuses on the actual knowledge of Kv channel expression and their relationship with neoplastic proliferation. In this work, we provide an update of what is currently known about these proteins, thereby paving the way for a more precise understanding of the participation of Kv during cancer development.

Proteasomes are a target of the anti-tumour drug vinblastine

2001 ◽  
Vol 356 (3) ◽  
pp. 835-841 ◽  
Author(s):  
Marco PICCININI ◽  
Ornella TAZARTES ◽  
Caterina MEZZATESTA ◽  
Emanuela RICOTTI ◽  
Stefano BEDINO ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Proteasome Inhibitors ◽  
Drug Dose ◽  
26S Proteasome ◽  
Cell Physiology ◽  
Cycle Progression ◽  
Hl60 Cells ◽  
Block Cell Cycle Progression

Proteasomes, the proteolytic machinery of the ubiquitin/ATP-dependent pathway, have a relevant role in many processes crucial for cell physiology and cell cycle progression. Proteasome inhibitors are used to block cell cycle progression and to induce apoptosis in certain cell lines. Here we examine whether proteasomal function is affected by the anti-tumour drug vinblastine, whose cytostatic action relies mainly on the disruption of mitotic spindle dynamics. The effects of vinblastine on the peptidase activities of human 20S and 26S proteasomes and on the proteolytic activity of 26S proteasome were assessed in the presence of specific fluorogenic peptides and 125I-lysozyme–ubiquitin conjugates respectively. The assays of ubiquitin–protein conjugates and of inhibitory κBα (IκBα), which are characteristic intracellular proteasome substrates, by Western blotting on lysates from HL60 cells incubated with or without vinblastine, illustrated the effects of vinblastine on proteasomes in vivo. We also evaluated the effects of vinblastine on the signal-induced degradation of IκBα. Vinblastine at 3–110μM reversibly inhibited the chymotrypsin-like activity of the 20 S proteasome and the trypsin-like and peptidyl-glutamyl-peptide hydrolysing activities of both proteasomes, but only at 110μM vinblastine was the chymotrypsin-like activity of the 26S proteasome inhibited; furthermore, at 25–200μM the drug inhibited the degradation of ubiquitinated lysozyme. In HL60 cells exposed for 6h to 0.5–10μM vinblastine, the drug-dose-related accumulation of polyubiquitinated proteins, as well as that of a high-molecular-mass form of IκBα, occurred. Moreover, vinblastine impaired the signal-induced degradation of IκBα. Cell viability throughout the test was approx. 95%. Proteasomes can be considered to be a new and additional vinblastine target.

Link between high-affinity adenosine concentrative nucleoside transporter-2 (CNT2) and energy metabolism in intestinal and liver parenchymal cells

2010 ◽  
Vol 225 (2) ◽  
pp. 620-630 ◽  
Author(s):  
Isabel Huber-Ruano ◽  
Itziar Pinilla-Macua ◽  
Gonzalo Torres ◽  
F. Javier Casado ◽  
Marçal Pastor-Anglada
Keyword(s):  
Energy Metabolism ◽  
Nucleoside Transporter ◽  
Liver Parenchymal ◽  
High Affinity ◽  
Concentrative Nucleoside Transporter ◽  
Parenchymal Cells

scholarly journals Hormonal regulation of concentrative nucleoside transport in liver parenchymal cells

1996 ◽  
Vol 313 (3) ◽  
pp. 915-920 ◽  
Author(s):  
Mireia GOMEZ-ANGELATS ◽  
Belén del SANTO ◽  
Joan MERCADER ◽  
Andreu FERRER-MARTINEZ ◽  
Antonio FELIPE ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cyclic Amp ◽  
Hormonal Regulation ◽  
Nucleoside Transporter ◽  
Dibutyryl Cyclic Amp ◽  
Liver Parenchymal ◽  
Uridine Uptake ◽  
Concentrative Nucleoside Transporter ◽  
Hormonal Modulation ◽  
Parenchymal Cells

Na+-dependent uridine uptake is stimulated in isolated rat liver parenchymal cells by glucagon. This effect is transient, reaches maximum levels of stimulation 10 min after hormone addition, and is dose-dependent. Glucagon action can be mimicked by agents that are able to hyperpolarize the plasma membrane (e.g. monensin) and by dibutyryl cyclic AMP. The effects triggered by glucagon, monensin and dibutyryl cyclic AMP are not additive, suggesting a common mechanism of action. 8-(4-Chlorophenylthio)adenosine 3´:5´-cyclic monophosphate (PCT), a cyclic AMP analogue but also a nucleoside analogue, markedly stimulates Na+-dependent uridine uptake in an additive manner to that triggered by monensin, similarly to the effect described for nitrobenzylthioinosine. Considering the roles reported for nucleosides in liver metabolism, the use of PCT as a cyclic AMP analogue should be precluded. Insulin is also able to up-regulate Na+-dependent uridine uptake by a mechanism which involves a stable induction of this transport activity at the plasma-membrane level. This is consistent with a mechanism involving synthesis and insertion of more carriers into the plasma membrane. It is concluded that the recently characterized hepatic concentrative nucleoside transporter is under short-term hormonal regulation by glucagon, through mechanisms which involve membrane hyperpolarization, and under long-term control by insulin. This is the first report showing hormonal modulation of the hepatic concentrative nucleoside transporter.

scholarly journals Equilibrative Nucleoside Transporter 2: Properties and Physiological Roles

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Safaa M. Naes ◽  
Sharaniza Ab-Rahim ◽  
Musalmah Mazlan ◽  
Amirah Abdul Rahman
Keyword(s):  
Cell Cycle Progression ◽  
Biological Membrane ◽  
Cell Types ◽  
Nucleoside Transporter ◽  
Potential Therapeutic Target ◽  
Cycle Progression ◽  
Equilibrative Nucleoside Transporter ◽  
Different Types ◽  
Advanced Stages

Equilibrative nucleoside transporter 2 (ENT2) is a bidirectional transporter embedded in the biological membrane and is ubiquitously found in most tissue and cell types. ENT2 mediates the uptake of purine and pyrimidine nucleosides and nucleobase besides transporting a variety of nucleoside-derived drugs, mostly in anticancer therapy. Since high expression of ENT2 has been correlated with advanced stages of different types of cancers, consequently, this has gained significant interest in the role of ENT2 as a potential therapeutic target. Furthermore, ENT2 plays critical roles in signaling pathway and cell cycle progression. Therefore, elucidating the physiological roles of ENT2 and its properties may contribute to a better understanding of ENT2 roles beyond their transportation mechanism. This review is aimed at highlighting the main roles of ENT2 and at providing a brief update on the recent research.

scholarly journals Human Cryptochrome Mediates Oxidative Stress Responses Modulated by Static and Electromagnetic Fields in Doxorubicin-Treated Cells

2020 ◽  
Author(s):  
Behnam Hajipour-Verdom ◽  
Mozhgan Alipour ◽  
Parviz Abdolmaleki ◽  
Saman Hosseinkhani ◽  
Mehdi Khoobi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Magnetic Fields ◽  
Stress Responses ◽  
Cell Cycle Progression ◽  
Excision Repair ◽  
Low Frequency ◽  
Moderate Intensity ◽  
Cell Physiology ◽  
Cycle Progression

Abstract Cryptochromes (CRYs) have been suggested to involve in the magnetic sensing for navigation of migratory birds in response to Earth’s magnetic fields. Magnetic fields (MFs) through wireless penetration change the cell physiology by effect on physicochemical reactions. Here, we aimed to investigate the behavior of HEK 293T cells overexpressing human CRY-based magnetoreception complexes undergo doxorubicin (DOX) treatment and exposure to moderate intensity static magnetic field (SMF) and extremely low frequency-pulsed electromagnetic field (ELF-PEMF). The ability of this magnetosensor is depended on CRY-photoreceptor proteins that complemented with putative magnetosensor proteins (MagR). The results indicate that magnetic sensitivity of CRY-based magnetosensor can effects on the intracellular reactive oxygen species (ROS) production and cell growth, cell cycle progression and expression of DNA damage-related genes due to treatment of DOX, SMF and ELF-PEMF. Our findings show that ROS accumulation significantly decreased in the cells expressing CRY/MagR complexes in response to all treatments, and also cell viability is decreased in contrast to MFs exposure. In addition, magnetosensitive complexes mediated the upregulation of genes in the base excision repair (BER) pathway including ITPA in presence of SMF as well as MTH1 in presence of ELF-PEMF in the DOX treated-cells. Furthermore, CRY/MagR induced a remarkable cell cycle arrest at G0/G1 phase in the all treatments. These results demonstrated that CRY/MagR complexes modify the DNA damage responses during genotoxic stresses by controlling the cell cycle progression and ROS levels. Therefore, our data suggest that CRY-based magnetosensitive complexes can increase the cytotoxic effects of DOX even when SMF and/or ELF-PEMF exposure were provided, exclusively.

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