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1.
Sensors (Basel) ; 24(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38931626

RESUMEN

This study introduces a flexible and low-cost solution for a source measure unit (SMU), which is presented as an alternative to conventional source meter units and a blueprint for sensor FET drivers. An SMU collects current-voltage (I-V) curves with an additional variable voltage or current and is commonly used to characterize semiconductors. We present the hardware design, interfacing, and test results of our SMU. Specifically, we present representative I-V curve measurements for graphene-channel FETs to demonstrate the SMU's capability to efficiently characterize these devices with minimal noise and sufficient accuracy. This cost-effective solution presents a promising avenue for researchers and developers seeking reliable tools for sensor development and characterization. We demonstrate, with the example of surface illumination, how the sensing behavior of graphene-channel FETs can be characterized without the need for expensive equipment. Additionally, the SMU was validated with known passive and active components, along with probe station integration for semiconductor die-scale connection. The SMU's focus on collecting I-V curves, coupled with its ability to identify device defects, such as parasitic Schottky junctions or a failed oxide, contributes to its utility in quality testing for semiconductor devices. Its low-cost nature makes it accessible for various research endeavors, enabling efficient data collection and analysis for graphene-based and other nanomaterial-based sensor applications.

2.
Sensors (Basel) ; 23(6)2023 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-36991948

RESUMEN

With the growing popularity of microgrids for alternative energy management, there is demand for tools that allow us to study the effect of microgrids in distributed power systems. Popular methods involve software simulation and prototype validation with physical hardware. Simulations often do not capture the complex interactions, and combinations of software simulations with hardware testbeds promise to give a more accurate picture. These testbeds, however, usually aim at the validation of hardware for industrial-scale use, which makes them expensive and not readily accessible. To fill the gap between full-scale hardware and software simulation, we propose a modular lab-scale grid model at a 1:100 power scale over residential single-phase networks with 12 V AC and 60 Hz grid voltage. We present different modules-power sources, inverters, demanders, grid monitors, and grid-to-grid bridges-that can be assembled into distributed grids of almost arbitrary complexity. The model voltage poses no electrical hazards, and microgrids can readily be assembled with an open power line model. Unlike a prior DC-based grid testbed, the proposed AC model allows us to examine additional aspects, such as frequency, phase, active and apparent power, and reactive loads. Grid metrics, including the discretely sampled voltage and current waveforms, can be collected and sent to higher-tier grid management systems. We integrated the modules with Beagle Bone micro-PCs, which in turn connect any such microgrid with an emulation platform built on CORE (Common Open Research Emulator) and the Gridlab-D power simulator, thereby allowing hybrid software/hardware simulations. Our grid modules were shown to fully operate in this environment. Through the CORE system, multitiered control and even remote grid management is possible. However, we also found that the AC waveform poses design challenges that require us to balance accurate emulation (most notably with respect to harmonic distortion) with per-module costs.

3.
SLAS Technol ; 25(3): 234-246, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31997709

RESUMEN

New insights into the biomechanical properties of cells are revealing the importance of these properties and how they relate to underlying molecular, architectural, and behavioral changes associated with cell state and disease processes. However, the current understanding of how these in vitro biomechanical properties are associated with in vivo processes has been developed based on the traditional monolayer (two-dimensional [2D]) cell culture, which traditionally has not translated well to the three-dimensional (3D) cell culture and in vivo function. Many gold standard methods and tools used to observe the biomechanical properties of 2D cell cultures cannot be used with 3D cell cultures. Fluorescent molecules can respond to external factors almost instantaneously and require relatively low-cost instrumentation. In this review, we provide the background on fluorescent molecular rotors, which are attractive tools due to the relationship of their emission quantum yield with environmental microviscosity. We make the case for their use in both 2D and 3D cell cultures and speculate on their fundamental and practical applications in cell biology.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Nanotecnología/instrumentación , Fenómenos Biomecánicos , Comunicación Celular , Microambiente Celular , Viscosidad
4.
ACS Biomater Sci Eng ; 6(7): 4314-4323, 2020 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-33463347

RESUMEN

In vitro screening for drugs that affect neural function in vivo is still primitive. It primarily relies on single cellular responses from 2D monolayer cultures that have been shown to be exaggerations of the in vivo response. For the 3D model to be physiologically relevant, it should express characteristics that not only differentiate it from 2D but also closely emulate those seen in vivo. These complex physiologically relevant (CPR) outcomes can serve as a standard for determining how close a 3D culture is to its native tissue or which out of a given number of 3D platforms is better suited for a given application. In this study, Fluo-4-based calcium fluorescence imaging was performed followed by automated image data processing to quantify the calcium oscillation frequency of SHSY5Y cells cultured in 2D and 3D formats. It was found that the calcium oscillation frequency is upregulated in traditional 2D cultures while it was comparable to in vivo in spheroid and microporous polymer scaffold-based 3D models, suggesting calcium oscillation frequency as a potential functional CPR indicator for neural cultures.


Asunto(s)
Técnicas de Cultivo de Célula , Neuroblastoma , Señalización del Calcio , Humanos
5.
Comput Biol Med ; 82: 40-48, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28160695

RESUMEN

X-ray images can suffer from excess contrast. Often, image exposure is chosen to visually optimize the region of interest, but at the expense of over- and underexposed regions elsewhere in the image. When image values are interpreted quantitatively as projected absorption, both over- and underexposure leads to the loss of quantitative information. We propose to combine multiple exposures into a composite that uses only pixels from those exposures in which they are neither under- nor overexposed. The composite image is created in analogy to visible-light high dynamic range photography. We present the mathematical framework for the recovery of absorbance from such composite images and demonstrate the method with biological and non-biological samples. We also show with an aluminum step-wedge that accurate recovery of step thickness from the absorbance values is possible, thereby highlighting the quantitative nature of the presented method. Due to the higher amount of detail encoded in an enhanced dynamic range x-ray image, we expect that the number of retaken images can be reduced, and patient exposure overall reduced. We also envision that the method can improve dual energy absorptiometry and even computed tomography by reducing the number of low-exposure ("photon-starved") projections.


Asunto(s)
Algoritmos , Enfermedades del Cabello/congénito , Intensificación de Imagen Radiográfica/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Radiografía/métodos , Animales , Gatos , Enfermedades del Cabello/diagnóstico por imagen , Humanos , Fantasmas de Imagen , Radiografía/instrumentación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
6.
J Mater Chem C Mater ; 4(14): 2707-2718, 2016 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-27127631

RESUMEN

Fluorescent molecules, with their almost instantaneous response to external influences and relatively low-cost measurement instrumentation, have been attractive analytical tools and biosensors for centuries. More recently, advanced chemical synthesis and targeted design have accelerated the development of fluorescent probes. This article focuses on dyes with segmental mobility (known as fluorescent molecular rotors) that act as mechanosensors, which are known for their relationship of emission quantum yield with microviscosity. Fluorescence lifetime is directly related to quantum yield, but steady-state emission intensity is not. To remove confounding factors with steady-state instrumentation, dual-band emission dyes can be used, and molecular rotors have been developed that either have intrinsic dual emission or that have a non-sensitive reference unit to provide a calibration emission band. We report on theory, chemical structure, applications and targeted design of several classes of dual-emission molecular rotors.

7.
Am J Vet Res ; 76(8): 667-78, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26207964

RESUMEN

UNLABELLED: OBJECTIVE :To develop a novel method for use of diagnostic imaging, finite element analysis (FEA), and simulated biomechanical response behavior of brain tissue in noninvasive assessment and estimation of intracranial pressure (ICP) of dogs. SAMPLE: MRI data for 5 dogs. PROCEDURES: MRI data for 5 dogs (1 with a geometrically normal brain that had no detectable signs of injury or disease and 4 with various degrees of geometric abnormalities) were obtained from a digital imaging archiving and communication system database. Patient-specific 3-D models composed of exact brain geometries were constructed from MRI images. Finite element analysis was used to simulate and observe patterns of nonlinear biphasic biomechanical response behavior of geometrically normal and abnormal canine brains at various levels of decreasing cerebral perfusion pressure and increasing ICP. RESULTS: Changes in biomechanical response behavior were detected with FEA for decreasing cerebral perfusion pressure and increasing ICP. Abnormalities in brain geometry led to observable changes in deformation and biomechanical response behavior for increased ICP, compared with results for geometrically normal brains. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, patient-specific critical ICP was identified, which could be useful as a method to predict the onset of brain herniation. Results indicated that it was feasible to apply FEA to brain geometry obtained from MRI data of clinical patients and to use biomechanical response behavior resulting from increased ICP as a diagnostic and prognostic method to noninvasively assess or classify levels of brain injury in clinical veterinary settings.


Asunto(s)
Encéfalo/fisiología , Enfermedades de los Perros/patología , Perros/fisiología , Hipertensión Intracraneal/veterinaria , Presión Intracraneal/fisiología , Animales , Fenómenos Biomecánicos , Encéfalo/patología , Enfermedades de los Perros/fisiopatología , Análisis de Elementos Finitos , Hipertensión Intracraneal/patología , Hipertensión Intracraneal/fisiopatología , Imagen por Resonancia Magnética/veterinaria
8.
Org Biomol Chem ; 13(10): 2965-73, 2015 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-25614187

RESUMEN

We describe the design, synthesis and fluorescent profile of a family of environment-sensitive dyes in which a dimethylamino (donor) group is conjugated to a cyanoacrylate (acceptor) unit via a cyclopenta[b]naphthalene ring system. This assembly satisfies the typical D-π-A motif of a fluorescent molecular rotor and exhibits solvatochromic and viscosity-sensitive fluorescence emission. The central naphthalene ring system of these dyes was synthesized via a novel intramolecular dehydrogenative dehydro-Diels-Alder (IDDDA) reaction that permits incorporation of the donor and acceptor groups in variable positions around the aromatic core. A bathochromic shift of excitation and emission peaks was observed with increasing solvent polarity but the dyes exhibited a complex emission pattern with a second red emission band when dissolved in nonpolar solvents. Consistent with other known molecular rotors, the emission intensity increased with increasing viscosity. Interestingly, closer spatial proximity between the donor and the acceptor groups led to decreased viscosity sensitivity combined with an increased quantum yield. This observation indicates that structural hindrance of intramolecular rotation dominates when the donor and acceptor groups are in close proximity. The examined compounds give insight into how excited state intramolecular rotation can be influenced by both the solvent and the chemical structure.


Asunto(s)
Cianoacrilatos/química , Colorantes Fluorescentes/química , Naftalenos/química , Reacción de Cicloadición , Diseño de Fármacos , Fluorescencia , Estructura Molecular , Solventes/química , Espectrometría de Fluorescencia , Viscosidad
9.
Biomed Instrum Technol ; 48(2): 142-51, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24712368

RESUMEN

Computed tomography (CT) scanners are expensive imaging devices, often out of reach for small research groups. Designing and building a CT scanner from modular components is possible, and this article demonstrates that realization of a CT scanner from components is surprisingly easy. However, the high costs of a modular X-ray source and detector limit the overall cost savings. In this article, the possibility of building a CT scanner with available surplus X-ray parts is discussed, and a practical device is described that incurred costs of less than $16,000. The image quality of this device is comparable with commercial devices. The disadvantage is that design constraints imposed by the available components lead to slow scan speeds and a resolution of 0.5 mm. Despite these limitations, a device such as this is attractive for imaging studies in the biological and biomedical sciences, as well as for advancing CT technology itself.

10.
J Biol Eng ; 7(1): 5, 2013 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-23421982

RESUMEN

BACKGROUND: Stink bugs represent a major agricultural pest complex attacking more than 200 wild and cultivated plants, including cotton in the southeastern US. Stink bug feeding on developing cotton bolls will cause boll abortion or lint staining and thus reduced yield and lint value. Current methods for stink bug detection involve manual harvesting and cracking open of a sizable number of immature cotton bolls for visual inspection. This process is cumbersome, time consuming, and requires a moderate level of experience to obtain accurate estimates. To improve detection of stink bug feeding, we present here a method based on fluorescent imaging and subsequent image analyses to determine the likelihood of stink bug damage in cotton bolls. RESULTS: Damage to different structures of cotton bolls including lint and carpal wall can be observed under blue LED-induced fluorescence. Generally speaking, damaged regions fluoresce green, whereas non-damaged regions with chlorophyll fluoresce red. However, similar fluorescence emission is also observable on cotton bolls that have not been fed upon by stink bugs. Criteria based on fluorescent intensity and the size of the fluorescent spot allow to differentiate between true positives (fluorescent regions associated with stink bug feeding) and false positives (fluorescent regions due to other causes). We found a detection rates with two combined criteria of 87% for true-positive marks and of 8% for false-positive marks. CONCLUSIONS: The imaging technique presented herein gives rise to a possible detection apparatus where a cotton boll is imaged in the field and images processed by software. The unique fluorescent signature left by stink bugs can be used to determine with high probability if a cotton boll has been punctured by a stink bug. We believe this technique, when integrated in a suitable device, could be used for more accurate detection in the field and allow for more optimized application of pest control.

11.
Bioorg Med Chem ; 20(14): 4443-50, 2012 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-22698784

RESUMEN

We describe the design, synthesis and fluorescence profiles of new self-calibrating viscosity dyes in which a coumarin (reference fluorophore) has been covalently linked with a molecular rotor (viscosity sensor). Characterization of their fluorescence properties was made with separate excitation of the units and through resonance energy transfer from the reference to the sensor dye. We have modified the linker and the substitution of the rotor in order to change the hydrophilicity of these probes thereby altering their subcellular localization. For instance, hydrophilic dye 12 shows a homogeneous distribution inside the cell and represents a suitable probe for viscosity measurements in the cytoplasm.


Asunto(s)
Transferencia Resonante de Energía de Fluorescencia , Colorantes Fluorescentes/química , Tiofenos/química , Calibración , Línea Celular Tumoral , Membrana Celular/metabolismo , Cumarinas/química , Transferencia Resonante de Energía de Fluorescencia/normas , Colorantes Fluorescentes/análisis , Colorantes Fluorescentes/síntesis química , Células HeLa , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía Confocal , Viscosidad
12.
J Fluoresc ; 22(1): 457-65, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21947609

RESUMEN

Molecular rotors are a group of environment-sensitive fluorescent probes whose quantum yield depends on the ability to form twisted intramolecular charge-transfer (TICT) states. TICT formation is dominantly governed by the solvent's microviscosity, but polarity and the ability of the solvent to form hydrogen bonds play an additional role. The relationship between quantum yield ϕ(F) and viscosity η is widely accepted as a power-law, ϕ(F) = C · η(x). In this study, we isolated the direct influence of the temperature on the TICT formation rate by examining several molecular rotors in protic and aprotic solvents over a range of temperatures. Each solvent's viscosity was determined as a function of temperature and used in the above power-law to determine how the proportionality constant C varies with temperature. We found that the power-law relationship fully explains the variations of the measured steady-state intensity by temperature-induced variations of the solvent viscosity, and C can be assumed to be temperature-independent. The exponent x, however, was found to be significantly higher in aprotic solvents than in protic solvents. We conclude that the ability of the solvent to form hydrogen bonds has a major influence on the relationship between viscosity and quantum yield. To use molecular rotors for the quantitative determination of viscosity or microviscosity, the exponent x needs to be determined for each dye-solvent combination.


Asunto(s)
Colorantes Fluorescentes/química , Rotación , Temperatura , Viscosidad
13.
J Biol Eng ; 5(1): 11, 2011 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-21816078

RESUMEN

BACKGROUND: Stink bugs (Hemiptera: Pentatomidae) comprise a critically important insect pest complex affecting 12 major crops worldwide including cotton. In the US, stink bug damage to developing cotton bolls causes boll abscission, lint staining, reduced fiber quality, and reduced yields with estimated losses ranging from 10 to 60 million dollars annually. Unfortunately, scouting for stink bug damage in the field is laborious and excessively time consuming. To improve scouting accuracy and efficiency, we investigated fluorescence changes in cotton boll tissues as a result of stink bug feeding. RESULTS: Fluorescent imaging under long-wave ultraviolet light showed that stink bug-damaged lint, the inner carpal wall, and the outside of the boll emitted strong blue-green fluorescence in a circular region near the puncture wound, whereas undamaged tissue emissions occurred at different wavelengths; the much weaker emission of undamaged tissue was dominated by chlorophyll fluorescence. We further characterized the optimum emission and excitation spectra to distinguish between stink bug damaged bolls from undamaged bolls. CONCLUSIONS: The observed characteristic fluorescence peaks associated with stink bug damage give rise to a fluorescence-based method to rapidly distinguish between undamaged and stink bug damaged cotton bolls. Based on the fluorescent fingerprint, we envision a fluorescence reflectance imaging or a fluorescence ratiometric device to assist pest management professionals with rapidly determining the extent of stink bug damage in a cotton field.

14.
Biochimie ; 93(6): 988-94, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21354253

RESUMEN

Molecular rotors are a form of fluorescent intramolecular charge-transfer complexes that can undergo intramolecular twisting motion upon photoexcitation. Twisted-state formation leads to non-radiative relaxation that competes with fluorescence emission. In bulk solutions, these molecules exhibit a viscosity-dependent quantum yield. On the molecular scale, the fluorescence emission is a function of the local free volume, which in turn is related to the local micro-viscosity. Membrane viscosity, and the inverse; fluidity, are characteristic terms used to describe the ease of movement withing the membrane. Often, changes in membrane viscosity govern intracellular processes and are indicative of a disease state. Molecular rotors have been used to investigate viscosity changes in liposomes and cells, but accuracy is affected by local concentration gradients and sample optical properties. We have developed self-calibrating ratiometric molecular rotors to overcome this challenge and integrated the new molecules into a DLPC liposome model exposed to the membrane-fluidizing agent propanol. We show that the ratiometric emission intensity linearly decreases with the propanol exposure and that the ratiometric intensity is widely independent of the total liposome concentration. Conversely, dye concentration inside liposomes influences the sensitivity of the system. We suggest that the new self-calibrating dyes can be used for real-time viscosity sensing in liposome systems with the advantages of lifetime measurements, but with low-cost steady-state instrumentation.


Asunto(s)
Cumarinas/química , Colorantes Fluorescentes/química , Liposomas/química , Tiofenos/química , 1-Propanol/química , Calibración , Cumarinas/síntesis química , Colorantes Fluorescentes/síntesis química , Humanos , Conformación Molecular , Fosfatidilcolinas/química , Sensibilidad y Especificidad , Espectrometría de Fluorescencia , Tiofenos/síntesis química , Viscosidad
15.
Org Biomol Chem ; 9(9): 3530-40, 2011 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-21437318

RESUMEN

We describe the design, synthesis and fluorescent profile of a family of self-calibrating dyes that provide ratiometric measurements of fluid viscosity. The design is based on covalently linking a primary fluorophore (reference) that displays a viscosity-independent fluorescence emission with a secondary fluorophore (sensor) that exhibits a viscosity-sensitive fluorescence emission. Characterization of fluorescent properties was made with separate excitation of the units and through Resonance Energy Transfer from the reference to the sensor dye. The chemical structures of both fluorophores and the linker length have been evaluated in order to optimize the overall brightness and sensitivity of the viscosity measurements. We also present an application of such ratiometric dyes for the detection of membrane viscosity changes in a liposome model.


Asunto(s)
Colorantes Fluorescentes/síntesis química , Calibración , Estructura Molecular , Viscosidad
16.
J Biol Eng ; 4: 11, 2010 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-20843326

RESUMEN

Molecular rotors are a group of fluorescent molecules that form twisted intramolecular charge transfer (TICT) states upon photoexcitation. When intramolecular twisting occurs, the molecular rotor returns to the ground state either by emission of a red-shifted emission band or by nonradiative relaxation. The emission properties are strongly solvent-dependent, and the solvent viscosity is the primary determinant of the fluorescent quantum yield from the planar (non-twisted) conformation. This viscosity-sensitive behavior gives rise to applications in, for example, fluid mechanics, polymer chemistry, cell physiology, and the food sciences. However, the relationship between bulk viscosity and the molecular-scale interaction of a molecular rotor with its environment are not fully understood. This review presents the pertinent theories of the rotor-solvent interaction on the molecular level and how this interaction leads to the viscosity-sensitive behavior. Furthermore, current applications of molecular rotors as microviscosity sensors are reviewed, and engineering aspects are presented on how measurement accuracy and precision can be improved.

17.
Tetrahedron ; 66(14): 2582-2588, 2010 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-20694175

RESUMEN

It has been shown that compounds containing the p-N,N,-dialkylaminobenzylidene cyanoacetate motif can serve as fluorescent non-mechanical viscosity sensors. These compounds, referred to as molecular rotors, belong to a class of fluorescent probes that are known to form twisted intramolecular charge-transfer complexes in the excited state. In this study we present the synthesis and spectroscopic characterization of these compounds as viscosity sensors. The effects of the molecular structure and electronic density of these rotors to the emission wavelength, fluorescence intensity and viscosity sensitivity are discussed.

18.
J Fluoresc ; 20(5): 1087-98, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20405175

RESUMEN

Molecular rotors are a group of fluorescent molecules that form twisted intramolecular charge transfer states (TICT) upon photoexcitation. Some classes of molecular rotors, among them those that are built on the benzylidene malononitrile motif, return to the ground state either by nonradiative intramolecular rotation or by fluorescence emission. In low-viscosity solvents, intramolecular rotation dominates, and the fluorescence quantum yield is low. Higher solvent viscosities reduce the intramolecular rotation rate, thus increasing the quantum yield. We recently described a different mechanism whereby the fluorescence quantum yield of the molecular rotor also depends on the shear stress of the solvent. In this study, we examined a possible application for shear-sensitive molecular rotors for imaging flow patterns in fluidic chambers. Flow chambers with different geometries were constructed from polycarbonate or acrylic. Solutions of molecular rotors in ethylene glycol were injected into the chamber under controlled flow rates. LED-induced fluorescence (LIF) images of the flow chambers were taken with a digital camera, and the intensity difference between flow and no-flow images was visualized and compared to computed fluid dynamics (CFD) simulations. Intensity differences were detectable with average flow rates as low as 0.1 mm/s, and an exponential association between flow rate and intensity increase was found. Furthermore, a good qualitative match to computed fluid dynamics simulations was seen. On the other hand, prolonged exposure to light reduced the emission intensity. With its high sensitivity and high spatial and temporal resolution, imaging of flow patterns with molecular rotors may become a useful tool in microfluidics, flow measurement, and control.


Asunto(s)
Colorantes/química , Colorantes Fluorescentes/química , Hidrodinámica , Procesamiento de Imagen Asistido por Computador , Sondas Moleculares/química , Simulación por Computador , Fluorescencia , Microfluídica/instrumentación , Sondas Moleculares/análisis , Estructura Molecular , Solventes/química , Espectrometría de Fluorescencia , Viscosidad
20.
J Lipid Res ; 51(5): 957-66, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19805624

RESUMEN

In the non-amyloidogenic pathway, amyloid precursor protein (APP) is cleaved by alpha-secretases to produce alpha-secretase-cleaved soluble APP (sAPP(alpha)) with neuroprotective and neurotrophic properties; therefore, enhancing the non-amyloidogenic pathway has been suggested as a potential pharmacological approach for the treatment of Alzheimer's disease. Here, we demonstrate the effects of type III secretory phospholipase A(2) (sPLA(2)-III) on sAPP(alpha) secretion. Exposing differentiated neuronal cells (SH-SY5Y cells and primary rat neurons) to sPLA(2)-III for 24 h increased sAPP(alpha) secretion and decreased levels of Abeta(1-42) in SH-SY5Y cells, and these changes were accompanied by increased membrane fluidity. We further tested whether sPLA(2)-III-enhanced sAPP(alpha) release is due in part to the production of its hydrolyzed products, including arachidonic acid (AA), palmitic acid (PA), and lysophosphatidylcholine (LPC). Addition of AA but neither PA nor LPC mimicked sPLA(2)-III-induced increases in sAPP(alpha) secretion and membrane fluidity. Treatment with sPLA(2)-III and AA increased accumulation of APP at the cell surface but did not alter total expressions of APP, alpha-secretases, and beta-site APP cleaving enzyme. Taken together, these results support the hypothesis that sPLA(2)-III enhances sAPP(alpha) secretion through its action to increase membrane fluidity and recruitment of APP at the cell surface.


Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Fosfolipasas A2 Grupo III/farmacología , Fluidez de la Membrana/efectos de los fármacos , Animales , Ácido Araquidónico/metabolismo , Ácido Araquidónico/farmacología , Ácido Aspártico Endopeptidasas/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Fosfolipasas A2 Grupo III/metabolismo , Humanos , Hidrólisis , Lisofosfatidilcolinas/metabolismo , Lisofosfatidilcolinas/farmacología , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacología , Ratas
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