A malignant cellular network in gliomas: potential clinical implications

Neuro-Oncology, Journal Year: 2016, Volume and Issue: 18(4), P. 479 - 485

Published: March 19, 2016

The recent discovery of distinct, ultra-long, and highly functional membrane protrusions in gliomas, particularly astrocytomas, extends our understanding how these tumors progress the brain they resist therapies. In this article, we will focus on ideas to target protrusions, for which have suggested term "tumor microtubes" (TMs), malignant multicellular network form. First, discuss TM-specific features their differential biological functions known so far. Second, connection between 1p/19q codeletion inability form TMs via certain neurodevelopmental pathways is presented; could provide an explanation distinct clinical oligodendrogliomas. Third, role primary potentially also adaptive resistance cytotoxic therapies highlighted. Fourth, avenues therapeutic approaches inhibit TM formation and/or function are discussed, with a disruption (or exploitation) functionality. Finally, propose use as biomarker glioma patients. An increasing preclinical settings show us whether really long-sought-after Achilles' heel treatment-resistant gliomas.

Language: Английский

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Cell-Autonomous Ca 2+ Flashes Elicit Pulsed Contractions of an Apical Actin Network to Drive Apical Constriction during Neural Tube Closure

Cell Reports, Journal Year: 2015, Volume and Issue: 13(10), P. 2189 - 2202

Published: Dec. 1, 2015

Neurulation is a critical period in all vertebrates and results the formation of neural tube, which gives rise to CNS. Apical constriction one fundamental morphogenetic movements that drives tube closure. Using live imaging, we show apical during neurulation stepwise process driven by cell-autonomous asynchronous contraction pulses followed stabilization steps. Our data suggest events are triggered Ca(2+) flashes transient contractile pool actin. In addition, provide evidence cell autonomy asynchrony required for correct spatial distribution and, as result, tissue morphogenesis. Finally, identify Calpain2 regulator it step, but dispensable contraction.

Language: Английский

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On the dynamical structure of calcium oscillations

Proceedings of the National Academy of Sciences, Journal Year: 2017, Volume and Issue: 114(7), P. 1456 - 1461

Published: Feb. 1, 2017

Significance Oscillations in the concentration of free cytosolic calcium are an important control mechanism many cell types. However, we still have little understanding how some cells can exhibit oscillations with a period less than second, whereas other hundreds seconds. Here, show that one common type oscillation has dynamic structure is independent period. We thus hypothesize their by varying rate at which critical internal variables move around this and be controlled activates release from endoplasmic/sarcoplasmic reticulum.

Language: Английский

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Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Glia, Journal Year: 2019, Volume and Issue: 68(1), P. 145 - 160

Published: Aug. 21, 2019

Astrocytes are important for information processing in the brain and they achieve this by fine-tuning neuronal communication via continuous uptake release of biochemical modulators neurotransmission synaptic plasticity. Often overlooked their functions mechanosensation. Indeed, astrocytes can detect pathophysiological changes mechanical properties injured, ageing, or degenerating tissue. We have recently shown that surrounding mechanically-stiff amyloid plaques upregulate mechanosensitive ion channel, Piezo1. Moreover, ageing transgenic Alzheimer's rats harboring a chronic peripheral bacterial infection displayed enhanced Piezo1 expression plaque-reactive hippocampus cerebral cortex. Here, we endotoxin, lipopolysaccharide (LPS), also upregulates primary mouse cortical astrocyte cultures vitro. Activation Piezo1, small molecule agonist Yoda1, Ca2+ influx both control LPS-stimulated astrocytes. Yoda1 augmented intracellular oscillations but decreased subsequent response to adenosine triphosphate (ATP) stimulation. Neither blocking nor activating affected cell viability. However, exposed activator, migrated significantly slower than reactive treated with channel-blocking peptide, GsMTx4. Furthermore, our data show channels inhibits cytokines chemokines, such as IL-1β, TNFα, fractalkine (CX3 CL1), from cultures. Taken together, results suggest astrocytic upregulation may act dampen neuroinflammation could be useful drug target neuroinflammatory disorders brain.

Language: Английский

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Connexins in the Heart: Regulation, Function and Involvement in Cardiac Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(9), P. 4413 - 4413

Published: April 23, 2021

Connexins are a family of transmembrane proteins that play key role in cardiac physiology. Gap junctional channels put into contact the cytoplasms connected cardiomyocytes, allowing existence electrical coupling. However, addition to this fundamental role, connexins also involved cardiomyocyte death and survival. Thus, chemical coupling through gap junctions plays spreading injury between cells. Moreover, their involvement cell-to-cell communication, mounting evidence indicates have additional junction-independent functions. Opening unopposed hemichannels, located at lateral surface may compromise cell homeostasis be ischemia/reperfusion injury. In addition, non-canonical structures, including mitochondria nucleus, been demonstrated cardioprotection regulation growth differentiation. review, we will provide, first, an overview on connexin biology, synthesis degradation, interactions. Then, conduct in-depth examination pathophysiology, new findings regarding myocardial injury, fibrosis, gene transcription or signaling regulation.

Language: Английский

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