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Results for “multifunction cell”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Identification and functional characterization of three type III polyketide synthases from Aquilaria sinensis calli

Type III polyketide synthases (PKSs) play an important role in biosynthesis of various plant secondary metabolites and plant adaptation to environmental stresses. Aquilaria sinensis (A. sinensis) is the main plant species for production of agarwood, little is known about its PKS family. In this study, AsCHS1 and two new type III PKSs, AsPKS1 and AsPKS2, were isolated and characterized in A. sinensis calli. The comparative sequence and phylogenetic analysis indicated that AsPKS1 and AsPKS2 belonged to non-CHS group different from AsCHS1. The recombinant AsPKS1 and AsPKS2 produced the lactone-type products, suggesting their different enzyme activities from AsCHS1. Three PKS genes had a tissues-specific pattern in A. sinensis. Moreover, we examined the expression profiles of three PKS genes in calli under different abiotic stresses and hormone treatments. AsCHS1 transcript was most significantly induced by salt stress, AsPKS1 abundance was most remarkably enhanced by CdCl{sub 2} treatment, while AsPKS2 expression was most significantly induced by mannitol treatment. Furthermore, AsCHS1, AsPKS1 and AsPKS2 expression was enhanced upon gibberellins (GA3), methyl jasmonate (MeJA), or salicylic acid (SA) treatment, while three PKS genes displayed low transcript levels at the early stage under abscisic acid (ABA) treatment. In addition, three GFP:PKSs fusion proteins were localized in the cytoplasm and cell wall in Nicotiana benthamiana cells. These results indicated the multifunctional role of three type III PKSs in polyketide biosynthesis, plant resistance to abiotic stresses and signal transduction. - Highlights: • Two new PKS genes (AsPKS1 and AsPKS2) were isolated and characterized from A. sinensis. • The recombinant AsPKS1 and AsPKS2 catalyzed lactone-type products in vitro. • AsCHS1, AsPKS1 and AsPKS2 were involved in plant responses to abiotic stresses and hormone stimuli. • Our results also indicated that AsCHS1, AsPKS1 and AsPKS2 were predominantly localized in the cytoplasm and cell wall.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Multifunctional entinostat enhances the mechanical robustness and efficiency of flexible perovskite solar cells and minimodules

Flexible perovskite solar cells (F-PSCs), prized for their nature of soft and high power-weight compatibility, have attracted intensive attention. However, inferior buried perovskite-substrate interfaces due to low interfacial adhesion between perovskites and substrates and large deformation of flexible substrates have greatly limited the performance of F-PSCs. Here, we add organic molecule Entinostat (ET) into hole extraction material Poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA) to enhance the adhesion at the perovskite/substrate interface using the interactions of ET with perovskites, PTAA and indium tin oxide (ITO) through its multiple function groups. Meanwhile, ET added into perovskites reduces the voids at the bottom perovskite film, due to its capability to tune the crystallization of perovskites by forming adduct with lead. Consequently, the inverted small area F-PSCs achieved an efficiency of 23.4%. The flexible perovskite minimodule with an area of 9 cm 2 achieved an aperture efficiency of ~19.0% certified by National Renewable Energy Laboratory. Furthermore, the optimized unencapsulated flexible minimodule retained 84% of the initial efficiency after 5000 bending cycles and retained 90% of the initial PCE (T90) after light soaking for >750 hours.

14 SOLAR ENERGY↗
DOE OSTI2024

Multifunctional Nanofiber Reinforcement for Improved Thermomechanical and Chemical Stability of Perovskite Solar Cells

This project focused on the development of metal halide perovskite-polymeric nanofiber nanocomposites for robust and efficient solar cells. Metal halide perovskite solar cells are a potentially disruptive technology with high efficiencies and low-cost solution processability amenable with roll-to-roll fabrication of flexible devices. However, perovskites exhibit extreme brittleness, high internal film stresses, and chemical instabilities that significantly limit service lifetimes under normal operating conditions. To date, most work addressing these shortcomings has been focused on encapsulating devices between thick layers of rigid materials such as glass, which increases the total weight and cost of devices. Furthermore, these rigid and heavy encapsulants do not translate well to emerging solar markets vital for national security, including integrated mobile power, emergency deployments for disaster relief and military engagement, and lightweight power for space. It is therefore critical to improve the thermomechanical and chemical stability of perovskite devices in a way that is compatible with flexible and lightweight substrates. In this project, we integrated nylon-6,6 nanofibers into MAPbI3 to mechanically reinforce the perovskite, demonstrating films that exhibited fracture energies 5-fold greater than pristine MAPbI3 while also maintaining similar power conversion efficiencies due to beneficial light scattering effects from the polymeric nanofibers. These results required successful development of approaches to control the deposition thickness of nanofiber mats down to 100s of nanometers, and to ensure the polymer nanofibers did not inhibit charge transport to the at the perovskite-transport layer interface.

14 SOLAR ENERGY↗
DOE OSTI2019

Performance improvement of proton exchange membrane electrolyzer cells by introducing in-plane transport enhancement layers

Thin/tunable liquid/gas diffusion layers (TT-LGDLs) or porous transport layers (TT-PTLs), have exhibited superior multifunctional performance in proton exchange membrane electrolyzer cells (PEMECs), which can be attributed to their unique structures, such as planar surface, straight-through pores, thin thickness, etc. For achieving better PEMEC performance, TT-LGDLs with smaller pore size are desired. However, in this case, mass diffusion issues are brought in when some of the pores are covered by the flow field lands or shoulders. The coverage of the pores can lead to very high transport resistance, which may reduce the number of active oxygen evolution reaction sites, and therefore lower down the PEMEC performance. The in-plane transport enhancement layer for TT-LGDLs/PTLs are proposed to develop a dual-layer LGDL/PTL structure for improving the mass diffusion and the PEMEC performance. The results of this research reveal that the dual-layer LGDL/PTL structure exhibits smaller ohmic resistance and mass transport resistance, and therefore improve the PEMEC performance, without obvious changes in kinetic losses. The total ohmic resistance and mass transport resistance can be reduced by about 23% and 41%, respectively, with an ~830 um pore TT-LGDL/PTL stacking on a ~100 um pore TT-LGDL/PTL. The results indicate the feasibility of stacking the in-plane transport enhancement layer with large pore sizes onto a small pore TT-LGDLs/PTLs for high efficiency and low cost PEMEC practical applications.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2018

DDX1 regulates alternative splicing and insulin secretion in pancreatic β cells

DEAD-box helicase 1 (DDX1) is a multifunction protein involved in diverse cellular processes including transcription, viral replication, mRNA/miRNA processing, and tRNA splicing. Here, we report a novel function of DDX1 in mRNA alternative splicing in pancreatic β cells. By performing integrated data analysis of high-throughput RNA sequencing (RNA-Seq), and cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq), we identify hundreds of alternative splicing genes that are targeted by DDX1. These DDX1-targeted alternative splicing genes are mainly associated with calcium ion binding, high voltage-gated calcium channel, and transmembrane transporter. Functionally, silencing DDX1 impairs calcium influx and insulin secretion in the pancreatic β cells. These results reveal an important role for DDX1 in the regulation of gene alternative splicing and insulin secretion in pancreatic β cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

CD147-induced cell proliferation is associated with Smad4 signal inhibition

CD147 is a multifunctional trans-membrane glycoprotein, which is highly expressed in many cancers. However, the mechanism by which CD147 modulates cell proliferation is not fully understood. The aim of this study is to investigate the role of CD147 in cell proliferation associated with the TGF-β/Smad4 signaling pathway. Here, we used cell viability and clone formation assays in LNCaP prostate cancer cells to demonstrate that CD147 promotes cell proliferation. The luciferase assay and western blotting show that silencing CD147 using shRNA enhances transcription and expression of p21{sup WAF1}. Using immunofluorescence and nuclear-cytoplasmic separation, we show that this is primarily attributed to transport of Smad4 from the cytoplasm to nucleus. Other assays (GST pull-down, co-immunoprecipitation and immunofluorescence) demonstrate that Smad4 is a new interaction partner of CD147, with the Smad4 MH2 domain and CD147 intracellular domain (CD147-ICD) being involved in the interaction. Furthermore, we report that a phosphoserine (pSer) in CD147 (pSer252) is responsible for this interaction and inhibition of the Smad4/p21{sup WAF1} signal that promotes cell proliferation. Our results provide a novel molecular mechanism for CD147-induced cell proliferation associated with Smad4 signal inhibition. - Highlights: • Smad4 interacts with CD147 via the MH2 domain. • CD147 prevents Smad4 translocation into the nuclear to regulate p21 transcription. • CD147 inhibits p21 transcription and expression independent on p53. • pCD147-S252 is responsible for interaction with Smad4 and p21 down-regulation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition

Integrin-linked kinase (ILK) is a multifunctional serine/threonine kinase. Accumulating evidences suggest that ILK are involved in cell–matrix interactions, cell proliferation, invasion, migration, angiogenesis and Epithelial–mesenchymal transition (EMT). However, the underlying mechanisms remain largely unknown. EMT has been postulated as a prerequisite for metastasis. The reports have demonstrated that EMT was implicated in metastasis of oral squamous cell carcinomas. Therefore, here we further postulate that ILK might participate in EMT of tongue cancer. We showed that ILK siRNA inhibited EMT with low N-cadherin, Vimentin, Snail, Slug and Twist as well as high E-cadherin expression in vivo and in vitro. We found that knockdown of ILK inhibited cell proliferation, migration and invasion as well as changed cell morphology. We also demonstrated that ILK siRNA inhibited phosphorylation of downstream signaling targets Akt and GSK3β as well as reduced expression of MMP2 and MMP9. Furthermore, we found that the tongue tumor with high metastasis capability showed higher ILK, Vimentin, Snail, Slug and Twist as well as lower E-cadherin expression in clinical specimens. Finally, ILK siRNA led to the suppression for tumorigenesis and metastasis in vivo. Our findings suggest that ILK could be a novel diagnostic and therapeutic target for tongue cancer. Highlights: • ILK siRNA influences cell morphology, cell cycle, migration and invasion. • ILK siRNA affects the expression of proteins associated with EMT. • ILK expression is related to EMT in clinical human tongue tumors. • ILK siRNA inhibits metastasis of the tongue cancer cells through suppressing EMT.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Leukemia inhibitory factor promotes extracellular matrix synthesis in degenerative nucleus pulposus cells via MAPK-ERK1/2 signaling pathway

Highlights: • LIF treatment was found to stimulate the synthesis of ECM in-vitro cultured NPCs. • LIF could activate the ERK1/2 signaling pathway to regulate ECM synthesis. • The therapeutic effect of LIF on deferring the degenerative process of disc was proved in vivo. Extracellular matrix (ECM) anabolism and catabolism imbalance is key feature of chondrocyte and intervertebral disc nucleus pulposus (NP) cell degeneration. The role of LIF as a multifunctional cytokine in the ECM metabolism of chondrocytes is controversial, but no relevant research in the ECM metabolism of NP cells. This study aimed to explore the biofunction and related mechanisms of LIF in the degenerative NP cells. We obtained an increase in the expression of LIF in the human degenerated NP specimens. The addition of recombinant human leukemia inhibitory factor (rhLIF) to the degenerated NP cells cultured in vitro was found to stimulate the synthesis of ECM, and rhLIF could activate the ERK1/2 signaling pathway. However, coculture with PD98059, a signal inhibitor of ERK1/2, blocked the effect of rhLIF on the synthesis of ECM. To furtherly clarify the role of LIF, we carried out animal experiments and found that rhLIF treatment could successfully delay the degree of degeneration of the intervertebral disc in a rabbit model; but with the addition of PD98059, the function of rhLIF for degeneration protection disappeared. In summary, this study demonstrates that LIF plays a role in promoting ECM synthesis in the degenerated NP cells as a protective role in intervertebral disc degeneration (IDD), which is related to the activation of ERK1/2 signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Leakless end-to-end transport of small molecules through micron-length DNA nanochannels

Designed and engineered protein and DNA nanopores can be used to sense and characterize single molecules and control transmembrane transport of molecular species. However, designed biomolecular pores are less than 100 nm in length and are used primarily for transport across lipid membranes. Nanochannels that span longer distances could be used as conduits for molecules between nonadjacent compartments or cells. We design micrometer-long, 7-nm-diameter DNA nanochannels that small molecules can traverse according to the laws of continuum diffusion. Binding DNA origami caps to channel ends eliminates transport and demonstrates that molecules diffuse from one channel end to the other rather than permeating through channel walls. These micrometer-length nanochannels can also grow, form interconnects, and interface with living cells. This work thus shows how to construct multifunctional, dynamic agents that control molecular transport, opening ways of studying intercellular signaling and modulating molecular transport between synthetic and living cells.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2008

Hydrogen Research for Spaceport and Space-Based Applications: Hydrogen Sensors and Systems

The activities presented are a broad based approach to advancing key hydrogen related technologies in areas such as fuel cells, hydrogen production, and distributed sensors for hydrogen-leak detection, laser instrumentation for hydrogen-leak detection, and cryogenic transport and storage. Presented are the results from research projects, education and outreach activities, system and trade studies. The work will aid in advancing the state-of-the-art for several critical technologies related to the implementation of a hydrogen infrastructure. Activities conducted are relevant to a number of propulsion and power systems for terrestrial, aeronautics and aerospace applications. Sensor systems research was focused on hydrogen leak detection and smart sensors with adaptive feedback control for fuel cells. The goal was to integrate multifunction smart sensors, low-power high-efficiency wireless circuits, energy harvesting devices, and power management circuits in one module. Activities were focused on testing and demonstrating sensors in a realistic environment while also bringing them closer to production and commercial viability for eventual use in the actual operating environment.

Anderson, Tim↗
DOE OSTI2018

Fully printed and integrated electrolyzer cells with additive manufacturing for high-efficiency water splitting

Using additive manufacturing (AM) technology, a fundamental material and structure innovation was proposed to significantly increase the energy efficiency, and to reduce the weight, volume and component quantity of proton exchange membrane electrolyzer cells (PEMECs). Four conventional parts (liquid/gas diffusion layer, bipolar plate, gasket, and current distributor) in a PEMEC were integrated into one multifunctional AM plate without committing to tools or molds for the first time. In addition, since the interfacial contact resistances between those parts were eliminated, the comprehensive in-situ characterizations of AM cells showed that an excellent energy efficiency of up to 86.48% was achieved at 2 A/cm2 and 80 degrees C, and the hydrogen generation rate was increased by 61.81% compared to the conventional cell. More importantly, the highly complex inner structures of the AM integrated multifunctional plates also exhibit the potential to break limitations of conventional manufacture methods for hydrogen generation and to open a door for the development of other energy conversion devices, including fuel cells, solar cells and batteries.

36 MATERIALS SCIENCE↗
DOE OSTI2017

Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices

The high density of the extracellular matrix in solid tumors is an important obstacle to nanocarriers for reaching deep tumor regions and has severely limited the efficacy of administrated nanotherapeutics. The use of proteolytic enzymes prior to nanoparticle administration or directly attached to the nanocarrier surface has been proposed to enhance their penetration, but the low in vivo stability of these macromolecules compromises their efficacy and strongly limits their application. Herein, we have designed a multifunctional nanocarrier able to transport cytotoxic drugs to deep areas of solid tumors and once there, to be engulfed by tumoral cells causing their destruction. This system is based on mesoporous silica nanocarriers encapsulated within supported lipid bilayers (SLBs). The SLB avoids premature release of the housed drug while providing high colloidal stability and an easy to functionalize surface. The tumor penetration property is provided by attachment of engineered polymeric nanocapsules that transport and controllably unveil and release the proteolytic enzymes that in turn digest the extracellular matrix, facilitating the nanocarrier diffusion through the matrix. Additionally, targeting properties were endowed by conjugating an antibody specific to the investigated tumoral cells to enhance binding, internalization, and drug delivery. This multifunctional design improves the therapeutic efficacy of the transported drug as a consequence of its more homogeneous distribution throughout the tumoral tissue.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Multifunction Hydrophobic Ligand Engineered Cd(S, Se)/ZnS Quantum Dots for Stabilizing Highly Efficient Carbon‐Based Perovskite Solar Cells

The long-term operational stability of perovskite solar cells (PSCs) remains a key challenge impeding their commercialization, particularly due to ambient environments (e.g., moisture, oxygen, heat)-induced degradation. Carbon electrode-based PSCs have emerged as cost-effective and relatively stable alternatives to metal electrode-based devices due to carbon materials' hydrophobic behavior, yet they still lag in both long-term durability and power conversion efficiency (PCE). In this work, an ultrathin hydrophobic ligand-modified core–shell Cd(S,Se)/ZnS quantum dots (QDs) capping layer is introduced as a multifunctional interfacial modifier for carbon-electrode-based PSCs. This oleic acid ligand-modified QDs capping layer exhibits inherent hydrophobicity, effectively serving as a moisture barrier to retard perovskite degradation under ambient conditions. Furthermore, the strong interfacial bonding between the QDs and perovskite halide surfaces leads to efficient trap state passivation, reducing trap density and creating a more uniform electrical contact. The modified QDs/perovskite interface also features an elevated conduction band edge, promoting improved charge extraction. As a result, devices incorporating this quantum dot capping layer retain 98% of their initial PCE after 450 h of ambient aging and achieve a champion efficiency of 20.74%. As a result, this strategy highlights the potential of hydrophobic ligand-modified chalcogenide QDs as surface modifiers to enhance both the stability and performance of carbon-based PSCs, offering a promising route toward scalable fabrication of durable perovskite solar modules.

14 SOLAR ENERGY↗
DOE OSTI2019

Patterning non-equilibrium morphologies in stimuli-responsive gels through topographical confinement

Stimuli-responsive “smart” polymers have generated significant interest for introducing dynamic control into the properties of antifouling coatings, smart membranes, switchable adhesives and cell manipulation substrates. Switchable surface morphologies formed by confining stimuli-responsive gels to topographically structured substrates have shown potential for a variety of interfacial applications. Beyond patterning the equilibrium swelling behavior of gels, subjecting stimuli-responsive gels to topographical confinement could also introduce spatial gradients in the various timescales associated with gel deformation, giving rise to novel non-equilibrium morphologies. In this work, we show how by curing poly(N-isopropylacrylamide) (pNIPAAm)-based gel under confinement to a rigid, bumpy substrate, we can not only induce the surface curvature to invert with temperature, but also program the transient, non-equilibrium morphologies that emerge during the inversion process through changing the heating path. Finite element simulations show that the emergence of these transient morphologies is correlated with confinement-induced gradients in polymer concentration and position-dependent hydrostatic pressure within the gel. To illustrate the relevance of such morphologies in interfacial applications, we show how they enable us to control the gravity-induced assembly of colloidal particles and microalgae. Finally, we show how more complex arrangements in particle assembly can be created through controlling the thickness of the temperature-responsive gel over the bumps. Patterning stimuli-responsive gels on topographically-structured surfaces not only enables switching between two invertible topographies, but could also create opportunities for stimuli ramp-dependent control over the local curvature of the surface and emergence of unique transient morphologies. Harnessing these features could have potential in the design of multifunctional, actuatable materials for switchable adhesion, antifouling, cell manipulation, and liquid and particle transport surfaces.

42 ENGINEERING↗
DOE OSTI2016

π-Conjugated Lewis Base: Efficient Trap-Passivation and Charge-Extraction for Hybrid Perovskite Solar Cells

Here, a π-conjugated Lewis base is introduced into perovskite solar cells, namely, indacenodithiophene end-capped with 1.1-dicyanomethylene-3-indanone (IDIC), as a multifunctional interlayer, which combines efficient trap-passivation and electron-extraction. Perovskite solar cells with IDIC layers yield higher photovoltages and photocurrents, and 45% enhanced efficiency compared with control devices without IDIC.

14 SOLAR ENERGY↗
DOE OSTI2018

Engineering the S-Layer of Caulobacter crescentus as a Foundation for Stable, High-Density, 2D Living Materials

Materials synthesized by organisms, such as bones and wood, combine the ability to self-repair with remarkable mechanical properties. This multifunctionality arises from the presence of living cells within the material and hierarchical assembly of different components across nanometer to micron scales. While creating engineered analogs of these natural materials is of growing interest, our ability to hierarchically order materials using living cells largely relies on engineered 1D protein filaments. Here, we lay the foundations for bottom-up assembly of engineered living material composites in 2D along the cell body using a synthetic biology approach. We engineer the paracrystalline surface-layer (S-layer) of Caulobacter crescentus to display SpyTag peptides that form irreversible isopeptide bonds to SpyCatcher-modified proteins, nanocrystals, and biopolymers on the extracellular surface. Using flow cytometry and confocal microscopy, we show that attachment of these materials to the cell surface is uniform, specific, and covalent, and its density can be controlled based on the location of the insertion within the S-layer protein, RsaA. Furthermore, we leverage the irreversible nature of this attachment to demonstrate via SDS-PAGE that the engineered S-layer can display a high density of materials, reaching 1 attachment site per 288 nm 2 . Lastly, we show that ligation of quantum dots to the cell surface does not impair cell viability and this composite material remains intact over a period of two weeks. Taken together, this work provides a platform for self-organization of soft and hard nanomaterials on a cell surface with precise control over 2D density, composition, and stability of the resulting composite, and is a key step towards building hierarchically-ordered engineered living materials with emergent properties.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Wip1 knockout inhibits the proliferation and enhances the migration of bone marrow mesenchymal stem cells

Mesenchymal stem cells (MSCs), a unique population of multipotent adult progenitor cells originally found in bone marrow (BM), are extremely useful for multifunctional therapeutic approaches. However, the growth arrest and premature senescence of MSCs in vitro prevent the in-depth characterization of these cells. In addition, the regulatory factors involved in MSCs migration remain largely unknown. Given that protein phosphorylation is associated with the processes of MSCs proliferation and migration, we focused on wild-type p53-inducible phosphatase-1 (Wip1), a well-studied modulator of phosphorylation, in this study. Our results showed that Wip1 knockout significantly inhibited MSCs proliferation and induced G2-phase cell-cycle arrest by reducing cyclinB1 expression. Compared with WT-MSCs, Wip1{sup −/−} MSCs displayed premature growth arrest after six passages in culture. Transwell and scratch assays revealed that Wip1{sup −/−} MSCs migrate more effectively than WT-MSCs. Moreover, the enhanced migratory response of Wip1{sup −/−} MSCs may be attributed to increases in the induction of Rac1-GTP activity, the pAKT/AKT ratio, the rearrangement of filamentous-actin (f-actin), and filopodia formation. Based on these results, we then examined the effect of treatment with a PI3K/AKT and Rac1 inhibitor, both of which impaired the migratory activity of MSCs. Therefore, we propose that the PI3K/AKT/Rac1 signaling axis mediates the Wip1 knockout-induced migration of MSCs. Our findings indicate that the principal function of Wip1 in MSCs transformation is the maintenance of proliferative capacity. Nevertheless, knocking out Wip1 increases the migratory capacity of MSCs. This dual effect of Wip1 provides the potential for purposeful routing of MSCs. - Highlights: • Wip1 knockout inhibited MSCs proliferation through reducing cyclinB1 expression. • Wip1{sup −/−} MSCs displayed premature growth arrest in vitro after six passages. • Knocking out Wip1 increases the migratory capacity of MSCs. • The PI3K/AKT/Rac1 pathway mediates the Wip1-knockout-induced migration of MSCs. • Overexpression of Wip1 reversed premature senescence and migration of Wip1{sup −/−} MSCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression

p300 is a multifunctional transcriptional coactivator that interacts with numerous transcription factors and exhibits protein/histone acetyltransferase activity. Loss of p300 function in humans and in mice leads to craniofacial defects. In this study, we demonstrated that inhibition of p300 histone acetyltransferase activity with the compound, C646, altered the expression of several genes, including Cdh1 (E-cadherin) in mouse maxillary mesenchyme cells, which are the cells that give rise to the secondary palate. The increased expression of plasma membrane-bound E-cadherin was associated with reduced cytosolic β-catenin, that led to attenuated signaling through the canonical Wnt pathway. Furthermore, C646 reduced both cell proliferation and the migratory ability of these cells. These results suggest that p300 histone acetyltransferase activity is critical for Wnt-dependent palate mesenchymal cell proliferation and migration, both processes that play a significant role in morphogenesis of the palate. - Highlights: • Inhibition of p300 HAT in cultured palate cells increased E-cadherin expression. • Inhibition of p300 HAT perturbed canonical Wnt signaling in cultured palate cells. • Blocking p300 HAT in palate cells altered rates of apoptosis, proliferation, and migration.

60 APPLIED LIFE SCIENCES↗