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Results for “Signal Transduction/physiology”

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 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Stromal cells can contribute oncogenic signals

The majority of studies of neoplastic transformation have focused attention on events that occur within transformed cells. These cell autonomous events result in the disruption of molecular pathways that regulate basic activities of the cells such as proliferation, death, movement and genomic integrity. Other studies have addressed the microenvironment of tumor cells and documented its importance in supporting tumor progression. Recent work has begun to expand on these initial studies of tumor microenvironment and now provide novel insights into the possible initiation and progression of malignant cells. This review will address the transforming effect of stromal cells on epithelial components. Copyright 2001 Academic Press.

Review↗
NASA NTRS2001

A role for inositol 1,4,5-trisphosphate in gravitropic signaling and the retention of cold-perceived gravistimulation of oat shoot pulvini

Plants sense positional changes relative to the gravity vector. To date, the signaling processes by which the perception of a gravistimulus is linked to the initiation of differential growth are poorly defined. We have investigated the role of inositol 1,4,5-trisphosphate (InsP(3)) in the gravitropic response of oat (Avena sativa) shoot pulvini. Within 15 s of gravistimulation, InsP(3) levels increased 3-fold over vertical controls in upper and lower pulvinus halves and fluctuated in both pulvinus halves over the first minutes. Between 10 and 30 min of gravistimulation, InsP(3) levels in the lower pulvinus half increased 3-fold over the upper. Changes in InsP(3) were confined to the pulvinus and were not detected in internodal tissue, highlighting the importance of the pulvinus for both graviperception and response. Inhibition of phospholipase C blocked the long-term increase in InsP(3), and reduced gravitropic bending by 65%. Short-term changes in InsP(3) were unimpaired by the inhibitor. Gravitropic bending of oat plants is inhibited at 4 degrees C; however, the plants retain the information of a positional change and respond at room temperature. Both short- and long-term changes in InsP(3) were present at 4 degrees C. We propose a role for InsP(3) in the establishment of tissue polarity during the gravitropic response of oat pulvini. InsP(3) may be involved in the retention of cold-perceived gravistimulation by providing positional information in the pulvini prior to the redistribution of auxin.

Non-NASA Center↗
NASA NTRS1999

Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

Non-NASA Center↗
NASA NTRS2000

Journey towards the centre of the earth: plant gravitropism

The study of gravitropism dates back about two hundred years, and although significant progress has been made in this field, the central question in gravitropism research is still unanswered. How is a physical stimulus transduced into a biochemical signal which ultimately elicits a response (curvature) in a plant? Simply put, how does a plant 'know' which way is down?.

NASA Discipline Plant Biology↗
NASA NTRS2001

Extracellular calcium sensing and extracellular calcium signaling

The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others, localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

Review↗
NASA NTRS2000

Mechanical control of cyclic AMP signalling and gene transcription through integrins

This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion or through specific transmembrane receptors, such as integrins? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.

NASA Discipline Cell Biology↗
NASA NTRS1999

Inertial processing of vestibulo-ocular signals

New evidence for a central resolution of gravito-inertial signals has been recently obtained by analyzing the properties of the vestibulo-ocular reflex (VOR) in response to combined lateral translations and roll tilts of the head. It is found that the VOR generates robust compensatory horizontal eye movements independent of whether or not the interaural translatory acceleration component is canceled out by a gravitational acceleration component due to simultaneous roll-tilt. This response property of the VOR depends on functional semicircular canals, suggesting that the brain uses both otolith and semicircular canal signals to estimate head motion relative to inertial space. Vestibular information about dynamic head attitude relative to gravity is the basis for computing head (and body) angular velocity relative to inertial space. Available evidence suggests that the inertial vestibular system controls both head attitude and velocity with respect to a gravity-centered reference frame. The basic computational principles underlying the inertial processing of otolith and semicircular canal afferent signals are outlined.

NASA Discipline Neuroscience↗
NASA NTRS1999

Signal processing related to the vestibulo-ocular reflex during combined angular rotation and linear translation of the head

The contributions of vestibular nerve afferents and central vestibular pathways to the angular (AVOR) and linear (LVOR) vestibulo-ocular reflex were studied in squirrel monkeys during fixation of near and far targets. Irregular vestibular afferents did not appear to be necessary for the LVOR, since when they were selectively silenced with galvanic currents the LVOR was essentially unaffected during both far- and near-target viewing. The linear translation signals generated by secondary AVOR neurons in the vestibular nuclei were, on average, in phase with head velocity, inversely related to viewing distance, and were nearly as strong as AVOR-related signals. We suggest that spatial-temporal transformation of linear head translation signals to angular eye velocity commands is accomplished primarily by the addition of viewing distance multiplied, centrally integrated, otolith regular afferent signals to angular VOR pathways.

NASA Discipline Neuroscience↗
NASA NTRS1999

Tensegrity and mechanoregulation: from skeleton to cytoskeleton

OBJECTIVE: To elucidate how mechanical stresses that are applied to the whole organism are transmitted to individual cells and transduced into a biochemical response. DESIGN: In this article, we describe fundamental design principles that are used to stabilize the musculoskeletal system at many different size scales and show that these design features are embodied in one particular form of architecture that is known as tensegrity. RESULTS: Tensegrity structures are characterized by use of continuous tension and local compression; architecture, prestress (internal stress prior to application of external force), and triangulation play the most critical roles in terms of determining their mechanical stability. In living organisms, use of a hierarchy of tensegrity networks both optimizes structural efficiency and provides a mechanism to mechanically couple the parts with the whole: mechanical stresses applied at the macroscale result in structural rearrangements at the cell and molecular level. CONCLUSION: Due to use of tensegrity architecture, mechanical stress is concentrated and focused on signal transducing molecules that physically associate with cell surface molecules that anchor cells to extracellular matrix, such as integrins, and with load-bearing elements within the internal cytoskeleton and nucleus. Mechanochemical transduction may then proceed through local stress-dependent changes in molecular mechanics, thermodynamics, and kinetics within the cell. In this manner, the entire cellular response to stress may be orchestrated and tuned by altering the prestress in the cell, just as changing muscular tone can alter mechanical stability and structural coordination throughout the whole musculoskeletal system.

NASA Discipline Cell Biology↗
NASA NTRS1998

Calcium-binding proteins and development

The known roles for calcium-binding proteins in developmental signaling pathways are reviewed. Current information on the calcium-binding characteristics of three classes of cell-surface developmental signaling proteins (EGF-domain proteins, cadherins and integrins) is presented together with an overview of the intracellular pathways downstream of these surface receptors. The developmental roles delineated to date for the universal intracellular calcium sensor, calmodulin, and its targets, and for calcium-binding regulators of the cytoskeleton are also reviewed.

Review↗
NASA NTRS1998

In search of cellular control: signal transduction in context

The field of molecular cell biology has experienced enormous advances over the last century by reducing the complexity of living cells into simpler molecular components and binding interactions that are amenable to rigorous biochemical analysis. However, as our tools become more powerful, there is a tendency to define mechanisms by what we can measure. The field is currently dominated by efforts to identify the key molecules and sequences that mediate the function of critical receptors, signal transducers, and molecular switches. Unfortunately, these conventional experimental approaches ignore the importance of supramolecular control mechanisms that play a critical role in cellular regulation. Thus, the significance of individual molecular constituents cannot be fully understood when studied in isolation because their function may vary depending on their context within the structural complexity of the living cell. These higher-order regulatory mechanisms are based on the cell's use of a form of solid-state biochemistry in which molecular components that mediate biochemical processing and signal transduction are immobilized on insoluble cytoskeletal scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of cellular regulation is the realization that chemistry is structure and hence, recognition of the the importance of architecture and mechanics for signal integration and biochemical control. Recent work that has unified chemical and mechanical signaling pathways provides a glimpse of how this form of higher-order cellular control may function and where paths may lie in the future.

Non-NASA Center↗
NASA NTRS1998

The molecular basis of ethylene signalling in Arabidopsis

The simple gas ethylene profoundly influences plants at nearly every stage of growth and development. In the past ten years, the use of a genetic approach, based on the triple response phenotype, has been a powerful tool for investigating the molecular events that underlie these effects. Several fundamental elements of the pathway have been described: a receptor with homology to bacterial two-component histidine kinases (ETR1), elements of a MAP kinase cascade (CTR1) and a putative transcription factor (EIN3). Taken together, these elements can be assembled into a simple, linear model for ethylene signalling that accounts for most of the well-characterized ethylene mediated responses.

Non-NASA Center↗
NASA NTRS1998

Recovery after exercise in the heat--factors influencing fluid intake

The restoration of body fluid balance following dehydration induced by exercise will occur through regulatory responses which stimulate ingestion of water and sodium ions. A number of different afferent signalling systems are necessary to generate appropriate thirst or sodium appetite. The primary sensory information of naturally occurring thirst is derived from receptors sensing cell volume and the volume of the extracellular fluid compartment. Sensory information from the oropharyngeal region is also an important determinant of thirst. The interaction of these various afferent signalling systems within the central nervous system determines the extent of fluid replacement following dehydration.

Non-NASA Center↗
NASA NTRS1998

Electrical signal transmission in a bone cell network: the influence of a discrete gap junction

A refined electrical cable model is formulated to investigate the role of a discrete gap junction in the intracellular transmission of electrical signals in an electrically coupled system of osteocytes and osteoblasts in an osteon. The model also examines the influence of the ratio q between the membrane's electrical time constant and the characteristic time of pore fluid pressure, the circular, cylindrical geometry of the osteon, and key simplifying assumptions in our earlier continuous cable model (see Zhang, D., S. C. Cowin, and S. Weinbaum. Electrical signal transmission and gap junction regulation in a bone cell network: A cable model for an osteon. Ann. Biomed. Eng. 25:379-396, 1997). Using this refined model, it is shown that (1) the intracellular potential amplitude at the osteoblastic end of the osteonal cable retains the character of a combination of a low-pass and a high-pass filter as the corner frequency varies in the physiological range; (2) the presence of a discrete gap junction near a resting osteoblast can lead to significant modulation of the intracellular potential and current in the osteoblast for measured values of the gap junction coupling strength; and (3) the circular, cylindrical geometry of the osteon is well simulated by the beam analogy used in Zhang et al.

Non-NASA Center↗
NASA NTRS1997

Yaw sensory rearrangement alters pitch vestibulo-ocular reflex responses

Ten male subjects underwent two types of adaptation paradigm designed either to enhance or to attenuate the gain of the canal-ocular reflex (COR), before undergoing otolith-ocular reflex (OOR) testing with constant velocity, earth horizontal axis and pitch rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about an earth vertical axis with a 0.2 Hz optokinetic stimulus that was deliberately mismatched in peak velocity or phase and was designed to produce short-term changes in the COR. Preadaptation and postadaptation OOR tests occurred at a constant velocity of 60 degrees/sec in the dark and produced a modulation component of the slow phase velocity with a frequency of 0.16 Hz due to otolithic stimulation by the sinusoidally changing gravity vector. Of the seven subjects who showed enhancement of the COR gain, six also showed enhancement of the OOR modulation component. Of the seven subjects who showed attenuation of the COR gain, five also showed attenuation of the OOR modulation component. The probability that these two cross-axis adaptation effects would occur by chance is less than 0.02. This suggests that visual-vestibular conditioning of the yaw axis COR also induced changes in the pitch axis OOR. We thus postulate that the central nervous system pathways that process horizontal canal yaw stimuli have elements in common with those processing otolithic stimuli about the pitch axis.

NASA Discipline Neuroscience↗
NASA NTRS1997

Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain

Mechanical force applied to bone produces two localized mechanical signals on the cell: deformation of the extracellular matrix (substrate strain) and extracellular fluid flow. To study the effects of these stimuli on osteoblasts, MC3T3-E1 cells were grown on type I collagen-coated plastic plates and subjected to four-point bending. This technique produces uniform levels of physiological strain and fluid forces on the cells. Each of these parameters can be varied independently. Osteopontin (OPN) mRNA expression was used to assess the anabolic response of MC3T3-E1 cells. When fluid forces were low, neither strain magnitude nor strain rate was correlated with OPN expression. However, higher-magnitude fluid forces significantly increased OPN message levels independently of the strain magnitude or rate. These data indicate that fluid forces, and not mechanical stretch, influence OPN expression in osteoblasts and suggest that fluid forces induced by extracellular fluid flow within the bone matrix may play an important role in bone formation in response to mechanical loading.

Non-NASA Center↗
NASA NTRS1997

Strain activation of bovine aortic smooth muscle cell proliferation and alignment: study of strain dependency and the role of protein kinase A and C signaling pathways

Smooth muscle cell (SMC) phenotype can be altered by physical forces as demonstrated by cyclic strain-induced changes in proliferation, orientation, and secretion of macromolecules. However, the magnitude of strain required and the intracellular coupling pathways remain ill defined. To examine the strain requirements for SMC proliferation, we selectively seeded bovine aortic SMC either on the center or periphery of silastic membranes which were deformed with 150 mm Hg vacuum (0-7% center; 7-24% periphery). SMC located in either the center or peripheral regions showed enhanced proliferation compared to cells grown under the absence of cyclic strain. Moreover, SMC located in the center region demonstrated significantly (P < 0.005) greater proliferation as compared to those in the periphery. In contrast, SMC exposed to high strain (7-24%) demonstrated alignment perpendicular to the strain gradient, whereas SMC in the center (0-7%) remained aligned randomly. To determine the mechanisms of these phenomena, we examined the effect of cyclic strain on bovine aortic SMC signaling pathways. We observed strain-induced stimulation of the cyclic AMP pathway including adenylate cyclase activity and cyclic AMP accumulation. In addition, exposure of SMC to cyclic strain caused a significant increase in protein kinase C (PKC) activity and enzyme translocation from the cytosol to a particulate fraction. Further study was conducted to examine the effect of strain magnitude on signaling, particularly protein kinase A (PKA) activity as well as cAMP response element (CRE) binding protein levels. We observed significantly (P < 0.05) greater PKA activity and CRE binding protein levels in SMC located in the center as compared to the peripheral region. However, inhibition of PKA (with 10 microM Rp-cAMP) or PKC (with 5-20 ng/ml staurosporine) failed to alter either the strain-induced increase in SMC proliferation or alignment. These data characterize the strain determinants for activation of SMC proliferation and alignment. Although strain activated both the AC/cAMP/PKA and the PKC pathways in SMC, singular inhibition of PKA and PKC failed to prevent strain-induced alignment and proliferation, suggesting either their lack of involvement or the multifactorial nature of these responses.

Non-NASA Center↗