FAM3A activates PI3K p110α/Akt signaling to ameliorate hepatic gluconeogenesis and lipogenesis DOI Open Access

Chunjiong Wang,

Yujing Chi, Jing Li

et al.

Hepatology, Journal Year: 2013, Volume and Issue: 59(5), P. 1779 - 1790

Published: Nov. 25, 2013

FAM3A belongs to a novel cytokine-like gene family, and its physiological role remains largely unknown. In our study, we found marked reduction of expression in the livers db/db high-fat diet (HFD)-induced diabetic mice. Hepatic overexpression markedly attenuated hyperglycemia, insulin resistance, fatty liver with increased Akt (pAkt) signaling repressed gluconeogenesis lipogenesis those contrast, small interfering RNA (siRNA)-mediated knockdown hepatic resulted hyperglycemia reduced pAkt levels C57BL/6 vitro study revealed that was mainly localized mitochondria, where it increases adenosine triphosphate (ATP) production secretion cultured hepatocytes. activated through p110α catalytic subunit PI3K an insulin-independent manner. Blockade P2 ATP receptors or downstream phospholipase C (PLC) IP3R removal medium calcium all significantly FAM3A-induced increase cytosolic free Ca2+ FAM3A-mediated PI3K/Akt activation. Moreover, activation completely abolished by inhibition calmodulin (CaM). Conclusion : plays crucial roles regulation glucose lipid metabolism liver, activates PI3K-Akt pathway way Ca2+/CaM-dependent mechanism. Up-regulating may represent attractive means for treatment type 2 diabetes, nonalcoholic disease (NAFLD). (Hepatology 2014;59:1779–1790)

Language: Английский

The biochemistry and function of pannexin channels DOI
Silvia Peñuela,

Ruchi Gehi,

Dale W. Laird

et al.

Biochimica et Biophysica Acta (BBA) - Biomembranes, Journal Year: 2012, Volume and Issue: 1828(1), P. 15 - 22

Published: Jan. 31, 2012

Language: Английский

Citations

360

Bone physiology as inspiration for tissue regenerative therapies DOI
Diana Lopes,

Cláudia Martins‐Cruz,

Mariana B. Oliveira

et al.

Biomaterials, Journal Year: 2018, Volume and Issue: 185, P. 240 - 275

Published: Sept. 17, 2018

Language: Английский

Citations

341

Intercellular Ca2+Waves: Mechanisms and Function DOI
Luc Leybaert, Michael J. Sanderson

Physiological Reviews, Journal Year: 2012, Volume and Issue: 92(3), P. 1359 - 1392

Published: July 1, 2012

Intercellular calcium (Ca 2+ ) waves (ICWs) represent the propagation of increases in intracellular Ca through a syncytium cells and appear to be fundamental mechanism for coordinating multicellular responses. ICWs occur wide diversity have been extensively studied vitro. More recent studies focus on vivo. are triggered by variety stimuli involve release from internal stores. The predominately involves cell communication with messengers moving via gap junctions or extracellular mediating paracrine signaling. important both normal physiology as well pathophysiological processes organs tissues including brain, liver, retina, cochlea, vascular tissue. We review here mechanisms initiation ICWs, key intra- (inositol 1,4,5-trisphosphate ATP) proposed physiological functions ICWs.

Language: Английский

Citations

291

Vesicular and conductive mechanisms of nucleotide release DOI
Eduardo R. Lazarowski

Purinergic Signalling, Journal Year: 2012, Volume and Issue: 8(3), P. 359 - 373

Published: April 12, 2012

Language: Английский

Citations

267

Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-ß-catenin DOI Creative Commons
Taifeng Zhou,

Bo Gao,

Yi Fan

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: March 18, 2020

Mechanical forces are fundamental regulators of cell behaviors. However, molecular regulation mechanotransduction remain poorly understood. Here, we identified the mechanosensitive channels Piezo1 and Piezo2 as key force sensors required for bone development osteoblast differentiation. Loss Piezo1, or more severely Piezo1/2, in mesenchymal progenitor cells, led to multiple spontaneous fractures newborn mice due inhibition differentiation increased resorption. In addition, loss Piezo1/2 rendered resistant further caused by unloading both homeostasis. Mechanistically, relayed fluid shear stress extracellular matrix stiffness signals activate Ca2+ influx stimulate Calcineurin, which promotes concerted activation NFATc1, YAP1 ß-catenin transcription factors inducing their dephosphorylation well NFAT/YAP1/ß-catenin complex formation. Yap1 activities were reduced mutant bones such defects partially rescued enhanced activities.

Language: Английский

Citations

256

ATP release through pannexon channels DOI Open Access
Gerhard Dahl

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2015, Volume and Issue: 370(1672), P. 20140191 - 20140191

Published: May 26, 2015

Extracellular adenosine triphosphate (ATP) serves as a signal for diverse physiological functions, including spread of calcium waves between astrocytes, control vascular oxygen supply and ciliary beat in the airways. ATP can be released from cells by various mechanisms. This review focuses on channel-mediated release its main enabler, Pannexin1 (Panx1). Six subunits Panx1 form plasma membrane channel termed ‘pannexon’. Depending mode stimulation, pannexon has large conductance (500 pS) unselective permeability to molecules less than 1.5 kD or is small (50 pS), chloride-selective channel. Most pathological stimuli induce conformation, whereas conformation so far only been observed with exclusive voltage activation The interaction pannexons intimate. not conduit ATP, permitting efflux down concentration gradient, but also modulated ATP. activated through both ionotropic P2X well metabotropic P2Y purinergic receptors. In absence mechanism, this positive feedback loop would lead cell death owing linkage receptors apoptotic processes. A mechanism preventing excessive provided binding (with low affinity) protein gating shut.

Language: Английский

Citations

224

ATP Release Channels DOI Open Access
Akiyuki Taruno

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(3), P. 808 - 808

Published: March 11, 2018

Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms cellular ATP release have demonstrated in many cell types. Although large negatively charged molecules cannot diffuse across lipid bilayer plasma membrane, conductive from cytosol into space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for permeation: anion permeability a ion-conducting pore. Currently, five groups are acknowledged ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1), volume-regulated (VRACs, also known volume-sensitive outwardly rectifying (VSOR) channels), maxi-anion (MACs). Recently, major breakthroughs made field by molecular identification CALHM1 action potential-dependent channel taste bud cells, LRRC8s components VRACs, SLCO2A1 core subunit MACs. Here, function roles these summarized, along discussion on future implications understanding

Language: Английский

Citations

175

Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis DOI Creative Commons
Siyu Zhu, Wei Chen,

Alasdair Masson

et al.

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 2, 2024

Abstract The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This process plays a crucial role in bone formation and homeostasis is regulated by two intricate processes: cell signal transduction transcriptional gene expression. Various essential signaling pathways, including Wnt, BMP, TGF-β, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, Piezo1/2, play critical facilitating osteoblast differentiation, formation, homeostasis. Key factors this include Runx2, Cbfβ, Runx1, Osterix, ATF4, SATB2, TAZ/YAP. Furthermore, diverse array epigenetic also roles at the level. review provides an overview latest developments current comprehension concerning pathways signaling, regulation hormones, genes involved commitment lineage, well maintenance paper reviews via mechanisms, such histone DNA modifications. Additionally, we summarize biology spurred recent advancements various modern technologies bioinformatics. By synthesizing these insights comprehensive understanding further clarification mechanisms underlying lineage commitment, highlights potential new therapeutic applications for treatment diseases.

Language: Английский

Citations

73

Biological role of connexin intercellular channels and hemichannels DOI
Rekha Kar,

Nidhi Batra,

Manuel A. Riquelme

et al.

Archives of Biochemistry and Biophysics, Journal Year: 2012, Volume and Issue: 524(1), P. 2 - 15

Published: March 17, 2012

Language: Английский

Citations

201

Gap-junction-mediated cell-to-cell communication DOI

Jean‐Claude Hervé,

Mickaël Derangeon

Cell and Tissue Research, Journal Year: 2012, Volume and Issue: 352(1), P. 21 - 31

Published: Aug. 31, 2012

Language: Английский

Citations

192