Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation

The Journal of Cell Biology, Journal Year: 2011, Volume and Issue: 193(7), P. 1257 - 1274

Published: June 20, 2011

The pannexin proteins represent a new gap junction family. However, the cellular functions of pannexins remain largely unknown. Here, we demonstrate that 3 (Panx3) promotes differentiation osteoblasts and ex vivo growth metatarsals. Panx3 expression was induced during osteogenic C2C12 cells primary calvarial cells, suppression this endogenous inhibited differentiation. functioned as unique Ca2+ channel in endoplasmic reticulum (ER), which activated by purinergic receptor/phosphoinositide 3-kinase (PI3K)/Akt signaling, followed activation calmodulin signaling for also formed hemichannels allowed release ATP into extracellular space receptors with subsequent PI3K–Akt signaling. junctions propagated waves between cells. Blocking activities osteoblast Thus, appears to be regulator functioning an ER hemichannel, forming junctions.

Language: Английский

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Flow detection and calcium signalling in vascular endothelial cells

Cardiovascular Research, Journal Year: 2013, Volume and Issue: 99(2), P. 260 - 268

Published: April 9, 2013

Blood vessels alter their morphology and function in response to changes blood flow, responses are based on flow detection by the vascular endothelium. Endothelial cells (ECs) covering inner surface of sense shear stress generated flowing transmit signal into interior cell, which evokes a cellular response. The EC is closely linked regulation tone, coagulation fibrinolysis, angiogenesis, remodelling, it plays an important role maintaining homoeostasis circulatory system. Impairment leads development diseases such as hypertension, thrombosis, aneurysms, atherosclerosis. Rapid progress has been made elucidating mechanotransduction using vitro methods that apply controlled levels cultured ECs fluid-dynamically designed flow-loading devices. results have revealed converted intracellular biochemical signals mediated variety membrane molecules microdomains, including ion channels, receptors, G-proteins, adhesion molecules, cytoskeleton, caveolae, glycocalyx, primary cilia, multiple downstream signalling pathways become activated almost simultaneously. Nevertheless, neither shear-stress-sensing mechanisms nor sensor initially yet known. Their identification would contribute better understanding pathophysiology occur flow-dependent manner new treatments for them.

Language: Английский

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Recent Advances in Application of Biosensors in Tissue Engineering

BioMed Research International, Journal Year: 2014, Volume and Issue: 2014, P. 1 - 18

Published: Jan. 1, 2014

Biosensors research is a fast growing field in which tens of thousands papers have been published over the years, and industry now worth billions dollars. The biosensor products found their applications numerous industries including food beverages, agricultural, environmental, medical diagnostics, pharmaceutical many more. Even though biosensors developed for detection proteins, peptides, enzymes, other biomolecules diverse applications, tissue engineering remained limited. In recent there has interest application novel cell culture engineering, example, real-time small molecules such as glucose, lactose, H 2 O well serum proteins large molecular size, albumin alpha-fetoprotein, inflammatory cytokines, IFN-g TNF- α . this review, we provide an overview advancements applications.

Language: Английский

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Strange attractors: DAMPs and autophagy link tumor cell death and immunity

Cell Death and Disease, Journal Year: 2013, Volume and Issue: 4(12), P. e966 - e966

Published: Dec. 12, 2013

Resistance to ‘apoptotic’ cell death is one of the major hallmarks cancer, contributing tumor development and therapeutic resistance. Damage-associated molecular patterns (DAMPs) are molecules released or exposed by dead, dying, injured, stressed non-apoptotic cells, with multiple roles in inflammation immunity. Release DAMPs not only contributes growth progression but also mediates skewing antitumor immunity during so-called immunogenic (ICD). Autophagy a lysosome-mediated homeostatic degradation process which cells digest their own effete organelles macromolecules meet bioenergetic needs enable protein synthesis. For autophagy double-edged sword. Autophagy, balance apoptosis, can function as suppressor; deficiency, associated alterations initiates tumorigenesis many settings. In contrast, autophagy-related stress tolerance generally promotes survival, enables Most anticancer therapies promote DAMP release enhance autophagy. regulates degradation, triggered regulated DAMPs. This interplay between DAMPs, serving ‘strange attractors’ dynamic system that emerges effectiveness treatment. shapes immune response dying upon ICD, culling least fit promoting survival others. Thus, suitable emergent targets for cancer therapy, considering more nuanced role progression.

Language: Английский

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Circadian Regulation of ATP Release in Astrocytes

Journal of Neuroscience, Journal Year: 2011, Volume and Issue: 31(23), P. 8342 - 8350

Published: June 8, 2011

Circadian clocks sustain daily oscillations in gene expression, physiology, and behavior, relying on transcription–translation feedback loops of clock genes for rhythm generation. Cultured astrocytes display extracellular ATP, suggesting that ATP release is a circadian output. We hypothesized the modulates via mechanisms regulate acute from glia. To test molecular basis release, we developed methods to measure real-time Bmal1::dLuc reporter expression cortical astrocyte cultures mice different genotypes. Daily rhythms required functional Clock Bmal1, both Per1 Per2, Cry1 Cry2 genes. Similarly, high-level, also mechanism. Whereas blocking IP₃ signaling significantly disrupted with no effect cycling, vesicular did not alter or expression. conclude depend express release.

Language: Английский

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Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

The Journal of Experimental Medicine, Journal Year: 2011, Volume and Issue: 208(9), P. 1823 - 1834

Published: Aug. 22, 2011

Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between envelope protein specific cell receptors. then acts on receptors, including P2Y2, to proline-rich tyrosine kinase 2 (Pyk2) transient depolarization, which in turn stimulate fusion Env-expressing membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition any constituents this cascade (pannexin-1, ATP, Pyk2) impairs replication mutant viruses are resistant conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved early steps infection may be targeted with new therapeutic approaches.

Language: Английский

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Mechanosensitive release of adenosine 5′‐triphosphate through pannexin channels and mechanosensitive upregulation of pannexin channels in optic nerve head astrocytes: A mechanism for purinergic involvement in chronic strain

Glia, Journal Year: 2014, Volume and Issue: 62(9), P. 1486 - 1501

Published: May 19, 2014

As adenosine 5′‐triphosphate (ATP) released from astrocytes can modulate many neural signaling systems, the triggers and pathways for this ATP release are important. Here, ability of mechanical strain to trigger through pannexin channels effects sustained on expression were examined in rat optic nerve head astrocytes. Astrocytes when subjected 5% equibiaxial or hypotonic swelling. Although expressed mRNA pannexins 1–3, connexin 43, VNUT, pharmacological analysis suggested a predominant role mechanosensitive release, with Rho kinase contribution. panx1 −/− mice had reduced baseline stimulated levels extracellular ATP, confirming pannexins. Swelling triggered regulatory volume decrease that was inhibited by apyrase probenecid. The swelling‐induced rise calcium P2X7 receptor antagonists A438079 AZ10606120, addition carbenoxolone. Extended stretch vitro upregulated panx2 mRNA. A similar upregulation observed vivo tissue Tg‐MYOC Y437H mouse model chronic glaucoma; genes , panx3 increased, whereas immunohistochemistry confirmed increased 1 protein. In summary, response strain, efflux pathway. Sustained . Together, these findings provide mechanism which remains elevated under as found patients glaucoma. GLIA 2014;62:1486–1501

Language: Английский

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Mechanosensitive pannexin-1 channels mediate microvascular metastatic cell survival

Nature Cell Biology, Journal Year: 2015, Volume and Issue: 17(7), P. 943 - 952

Published: June 22, 2015

Language: Английский

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Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development

EBioMedicine, Journal Year: 2020, Volume and Issue: 55, P. 102768 - 102768

Published: April 16, 2020

The pandemic spread of a novel coronavirus – SARS coronavirus-2 (SARS-CoV-2) as cause acute respiratory illness, named Covid-19, is placing the healthcare systems many countries under unprecedented stress. Global economies are also spiraling towards recession in fear this new life-threatening disease. Vaccines that prevent SARS-CoV-2 infection and therapeutics reduces risk severe Covid-19 thus urgently needed. A rapid method to derive antiviral treatment for use convalescent plasma derived hyperimmune globulin. However, both globulin vaccine development face common hurdle antibody-mediated disease enhancement. goal review examine body evidence supporting hypothesis immune enhancement could be pertinent Covid-19. We discuss how mitigated so vaccines rapidly translated overcome current global health crisis.

Language: Английский

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Manipulating cell fate: dynamic control of cell behaviors on functional platforms

Chemical Society Reviews, Journal Year: 2018, Volume and Issue: 47(23), P. 8639 - 8684

Published: Jan. 1, 2018

The cell microenvironment choreographs the behaviors of cells through multiple well-controlled signals. For basic biological study and cell-based therapies, it is essential to decipher complicated cell-matrix interactions, develop ways mimic dynamic so that desired functions can be guided. this, biomaterials with ability spatiotemporally impart biochemical biophysical cues manipulate fate have been developed recently. property programmable features stimuli-responsive biointerfaces endow them outstanding advanced systems. In this review, we illustrate recent progress biosystems a particular emphasis on their explorations for fundamental studies, disease diagnosis regenerative therapy. Some principles strategies design platforms are also discussed in review. Finally, conclude an outlook current challenges future biomedical applications. Overall, anticipate review will boost development multifunctional by inspiring interest from various disciplines, including chemistry, materials science, biology, nanotechnology, engineering, as well clinical research.

Language: Английский

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