Disulfiram modulated ROS–MAPK and NF κ B pathways and targeted breast cancer cells with cancer stem cell-like properties

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Disulfiram modulated ROS-MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties.

Stem cells possess the dual properties of self-renewal and pluripotency. Self-renewal affords these populations the luxury of self-propagation, whereas pluripotency allows them to produce the multitude of cell types found in the body. Protection of the stem cell population from damage or death is critical because these cells need to remain intact throughout the life of an organism. The principal mechanism of protection is through expression of multifunctional efflux transporters—the adenosine triphosphate–binding cassette (ABC) transporters that are the “guardians” of the stem cell population. Ironically, it has been shown that these ABC efflux pumps also afford protection to cancer stem cells (CSCs), shielding them from the adverse effects of chemotherapeutic insult. It is therefore imperative to gain a better understanding of the mechanisms involved in the resistance of stem cells to chemotherapy, which could lead to the discovery of new therapeutic targets and improvement of current anticancer strategies.



Clinical Pharmacology & Therapeutics (2011) 89 4, 491–502. doi:10.1038/clpt.2011.14

Multidrug Efflux Pumps and Cancer Stem Cells: Insights Into Multidrug Resistance and Therapeutic Development

Cardiac and skeletal striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity. The sarcomere is comprised of precisely organized individual filament systems that include thin (actin), thick (myosin), titin, and nebulin. Connecting the sarcomere to other organelles (e.g., mitochondria and nucleus) and serving as the scaffold to maintain cellular integrity are the intermediate filaments. The costamere, on the other hand, tethers the sarcomere to the cell membrane. Unique structures like the intercalated disc in cardiac muscle and the myotendinous junction in skeletal muscle help synchronize and transmit force. Intense investigation has been done on many of the proteins that make up these cytoskeletal assemblies. Yet the details of their function and how they interconnect have just started to be elucidated. A vast number of human myopathies are contributed to mutations in muscle proteins; thus understanding their basic function provides a mechanistic understanding of muscle disorders. In this review, we highlight the components of striated muscle with respect to their interactions, signaling pathways, functions, and connections to disease. © 2017 American Physiological Society. Compr Physiol 7:891-944, 2017.

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Overview of the Muscle Cytoskeleton.

The growth hormone receptor (GHR), although most well known for regulating growth, has many other important biological functions including regulating metabolism and controlling physiological processes related to the hepatobiliary, cardiovascular, renal, gastrointestinal, and reproductive systems. In addition, growth hormone signaling is an important regulator of aging and plays a significant role in cancer development. Growth hormone activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, and recent studies have provided a new understanding of the mechanism of JAK2 activation by growth hormone binding to its receptor. JAK2 activation is required for growth hormone-mediated activation of STAT1, STAT3, and STAT5, and the negative regulation of JAK-STAT signaling comprises an important step in the control of this signaling pathway. The GHR also activates the Src family kinase signaling pathway independent of JAK2. This review covers the molecular mechanisms of GHR activation and signal transduction as well as the physiological consequences of growth hormone signaling.

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The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects

The high resolution X-Ray Spectrometer (XRS) has been designed to provide the Suzaku Observatory with very high spectral resolution, non-dispersive spectroscopy from 0.3 to 12 keV. This energy range encompasses the most diagnostically-rich part of the x-ray band. The sensor consists of a 32 channel array of x-ray of microcalorimeters, each with an energy resolution of about 6 eV. The very low temperature required for operation of the array (60 mK) is provided by a four-stage cooling system containing a single stage ADR, superfluid He Cryostat, solid Ne Dewar, and a single-stage Stirling-cycle cooler. The Suzaku/XRS is the first orbiting x-ray microcalorimeter spectrometer and has been designed to last more than three years in orbit. The early verification phase of the mission demonstrated that the instrument was working properly and that the cryogen consumption rate was low enough to ensure a mission lifetime exceeding 3 years. However, the liquid He cryogen was completely vaporized two weeks after opening the dewar guard vacuum vent. The problem has been traced to inadequate venting of the dewar He and Ne gases out of the spacecraft into space. In this paper we present the design of the XRS instrument and describe the in-flight performance.

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The Suzaku High Resolution X-Ray Spectrometer

http://www.inct-ta.furg.br/english/producao/262010.pdf

Relationships between multidrug resistance (MDR) and stem cell markers in human chronic myeloid leukemia cell lines

Different physiological mechanisms control isovolumetric regulation and regulatory volume decrease in chick embryo cardiomyocytes.

Cytotoxicity of the association of pesticides Roundup Transorb® and Furadan 350 SC® on the zebrafish cell line, ZF-L

We used immunocytochemical and fluorometric techniques to show that gill cells of two marine inverte- brates, the crab Neohelice granulata (osmoregulator) and the clam Mesodesma mactroides (osmoconformer), increase the expression of membrane transporters (Na ? /K ? -ATPase and aquaporin (AQP1)) after whole-animals exposure (96 h) to sublethal concentrations of copper in water of salinity 30 ppt, when both clams and crabs are isosmotic with respect to the environmental medium. A plausible inter- pretation of our findings is that this increased expression in membrane transporters may serve as an attempt to amelio- rate the deleterious effects of copper on the mechanisms involved in ion and volume regulation in gill cells.

The effects of copper on Na(+)/K (+)-ATPase and aquaporin expression in two euryhaline invertebrates.

Chromatic adaptation in crustaceans results from the differential distribution of colored pigment granules within their chromatophores consequent to cell signaling by neurosecretory peptides. However, the force transducing, mechanochemical protein motors responsible for granule translocation, and their molecular mechanisms of action, are not well understood. The present study uses immunocytochemical techniques and a motility assay in vitro to demonstrate that protein motors from the kinesin and myosin superfamilies are stably associated with membrane-bounded pigment granules in the red, ovarian chromatophores of the freshwater, palaemonid shrimp, Macrobrachium olfersii. Monoclonal antibodies against conventional kinesin heavy chain, and an anti-myosin whole serum, labeled pigment-containing fragments prepared from homogenates of chromatophores with fully dispersed or aggregated pigments: this finding infers a permanent association between the protein motors and the pigment granules, and suggests that such motors may be regulated while bound to their cargos. The pigment aggregator appears to be a myosin since the anti-myosin whole serum attenuated hormonally triggered pigment aggregation in the motility assay in vitro, and induced pigment hyper-dispersion in some chromatophores. Western blots of the chromatophore-containing, ovarian tissue homogenate demonstrated protein bands consistent with myosin II and myosin XII, either of which may be the pigment aggregator. This study provides the first direct evidence for myosin and kinesin protein motors directly and stably associated with pigment granules in crustacean chromatophores, and may represent the first successful isolation of myosin class XII.

Robert Tew Boyle

Papers

Relationships between multidrug resistance (MDR) and stem cell markers in human chronic myeloid leukemia cell lines

Different physiological mechanisms control isovolumetric regulation and regulatory volume decrease in chick embryo cardiomyocytes.

Cytotoxicity of the association of pesticides Roundup Transorb® and Furadan 350 SC® on the zebrafish cell line, ZF-L

The effects of copper on Na(+)/K (+)-ATPase and aquaporin expression in two euryhaline invertebrates.

Association of kinesin and myosin with pigment granules in crustacean chromatophores.