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Yes‐associated protein (YAP) and its paralog WW domain containing transcription regulator 1 (TAZ) are important regulators of multiple cellular functions such as proliferation, differentiation, and survival. On the tissue level, YAP/TAZ... more
Yes‐associated protein (YAP) and its paralog WW domain containing transcription regulator 1 (TAZ) are important regulators of multiple cellular functions such as proliferation, differentiation, and survival. On the tissue level, YAP/TAZ are essential for embryonic development, organ size control and regeneration, while their deregulation leads to carcinogenesis or other diseases. As an underlying principle for YAP/TAZ‐mediated regulation of biological functions, a growing body of research reveals that YAP/TAZ play a central role in delivering information of mechanical environments surrounding cells to the nucleus transcriptional machinery. In this review, we discuss mechanical cue‐dependent regulatory mechanisms for YAP/TAZ functions, as well as their clinical significance in cancer progression and treatment.
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We previously reported that SAK(CA), a stretch-activated, large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channel is present in chick embryonic heart. Here, we cloned SAK(CA) and identified that Stress-Axis Regulated... more
We previously reported that SAK(CA), a stretch-activated, large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channel is present in chick embryonic heart. Here, we cloned SAK(CA) and identified that Stress-Axis Regulated Exon (STREX) is responsible for the stretch sensitivity. Single patch-clamp recordings from CHO cells transfected with the cloned SAK(CA) showed stretch sensitivity, whereas deletion of the STREX insert diminished the stretch sensitivity of the channel. Sequence analysis revealed that the ERA (672-674) sequence of the STREX is indispensable for channel stretch sensitivity and single amino acid substitution from Ala674 to Thr674 completely eliminated the stretch sensitivity. Co-expression of chick STREX-EGFP and SAK(CA) in CHO cells, induced a strong GFP signal in the cell membrane and inhibited the stretch sensitivity significantly. These results suggest that SAK(CA) senses membrane tension through an interaction between STREX and submembranous components.
Research Interests: Biophysics, Chemistry, Medicine, Sequence Analysis, Cellular mechanotransduction, and 15 moreAnimals, Heart, Potassium, Mechanical Stress, Transfection, Amino Acid Sequence, Amino Acid Substitution Rates, Patch Clamp, Biochemistry and cell biology, Molecular Sequence Data, Cell Membrane, CHO cells, Cricetinae, Chick embryo, and Medical biochemistry and metabolomics
Research Interests: Pharmacology, Medicine, Neuroprotection, Ischemia, Animals, and 15 moreMale, Cell Death, Neurotoxicity, Brain Ischemia, Clinical Sciences, Rats, Neuronal Death, Cerebral Ischemia, Dehydroepiandrosterone, Memory Disorders, Neurosciences, Brain Damage, Neuroprotective Agents, NMDA receptor, and Cardiovascular medicine and haematology
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Superoxide production in response to cyclic stretch (1 Hz, 20% in length) was investigated in human umbilical vein endothelial cells (HUVECs). The basal production of superoxide without stretch increased gradually, while the production of... more
Superoxide production in response to cyclic stretch (1 Hz, 20% in length) was investigated in human umbilical vein endothelial cells (HUVECs). The basal production of superoxide without stretch increased gradually, while the production of superoxide with stretch increased significantly as compared to that without stretch and it became significant 80 min after the onset of cyclic stretch (P<0.05, n=8-14). The superoxide production increased in a stretch-dependent manner and became significant when stretch was more than 10% (p<0.05, n=11-16). To investigate the involvement of SA channel, we added Gd3+ or EGTA in the reaction solution and examined the stretch-induced superoxide production. In cells stretched in the presence of 20 microM Gd3+, the stretch-induced superoxide production was significantly inhibited (at 120 min, p<0.05, n=8-18). The cyclic stretch-induced superoxide production was also significantly inhibited by the removal of extracellular Ca2+ with 5 mM EGTA (at 120 min, p<0.05, n=8-18). Neither the application of Gd3+ nor the removal of extracellular Ca2+ significantly changed the basal production of superoxide. These data suggest that the stretch-induced superoxide production increases in time- and stretch-dependent manner and that the stretch-induced superoxide production in HUVECs is regulated by Ca2+ influx through SA channels.
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Research Interests: Mechanical Engineering, Materials Science, Biomedical Engineering, Biomechanics, Cytoskeleton, and 15 moreMechanical properties, Humans, Computer Simulation, Cell Mechanics, Animals, Computational Biomechanics, Actin, Actin Cytoskeleton, Actin Dynamics, Chickens, Large Scale, MD Simulation, Actin Filaments, Adenosine Diphosphate, and Biomechanical Phenomena
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Research Interests: Neuroscience, Psychology, Computer Science, Physics, Magnetic Resonance Imaging, and 15 moreMedicine, Executive Function, Humans, Cues, Functional Magnetic Resonance Imaging, Female, Neuroimage, Male, Motor Cortex, Premotor cortex, Precuneus, Adult, Parietal Lobe, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Chemistry, Calcium, Cell Biology, Medicine, Humans, and 15 moreAnimals, Mechanoreceptors, Phosphorylation, Mitogen Activated Protein Kinase, Kinase, Rats, Phenylalanine, Transfection, Extracellular, Biochemistry and cell biology, Focal Adhesion Kinase, Cell Membrane, fibroblasts, Protein tyrosine kinases, and Medical biochemistry and metabolomics
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The neurosteroid dehydroepiandrosterone-sulfate (DHEAS) is a positive modulator of synaptic transmission in mammalian brains; however, the underlying molecular mechanisms are not fully understood. This report describes the acute effects... more
The neurosteroid dehydroepiandrosterone-sulfate (DHEAS) is a positive modulator of synaptic transmission in mammalian brains; however, the underlying molecular mechanisms are not fully understood. This report describes the acute effects of DHEAS on the synaptic transmission in the hippocampal dentate gyrus of rat brain slices. The application of DHEAS for 10 min augmented the optically recorded EPSP (op-EPSP) in a dose dependent manner. The effect became visible at 1 nM and saturated at 100 nM. We focused on the effect of DHEAS at 100 nM, where the op-EPSP amplitude was increased by 30%, and gradually decreased to the basal level in 30 min after wash out of the drug (short-term potentiation by DHEAS; STP(DHEAS)). DHEAS did not alter the presynaptic properties including the presynaptic fiber volley (PSFV) and paired pulse facilitation (PPF), thus indicating that the acute DHEAS effect is of postsynaptic origin. The involvement of putative DHEAS targets, GABA(A), NMDA, and σ1 receptors in STP(DHEAS) was also investigated; however, antagonists to these receptors only partially inhibited the acute effect of DHEAS. By contrast, STP(DHEAS) was totally inhibited by either the metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP (10 μM) or the ryanodine receptor (RyR) inhibitors (ryanodine and ruthenium red), but not by the mGluR1 antagonist LY367385 and the IP3R antagonist 2-APB, suggesting that STP(DHEAS) is mediated by an mGluR5-RyR cascade in postsynaptic neurons. Consistent with this finding, the selective agonist for mGluR5 CHPG nearly perfectly mimicked the DHEAS effect. This is the first demonstration of mGluR involvement in the DHEAS action in regard to hippocampal synaptic transmission.
Research Interests: Endocrinology, Cognitive Science, Chemistry, Long Term Potentiation, Medicine, and 15 moreSignal Transduction, Hippocampus, Internal Medicine, Animals, Male, Calcium Signaling, Synaptic Transmission, Dentate Gyrus, Rats, Wistar Rats, Glycine, Neurosciences, Excitatory Postsynaptic Potentials, Electric stimulation, and dehydroepiandrosterone sulfate
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Skeletal muscle cells are hypertrophied by mechanical stresses, but the underlying molecular mechanisms are not fully understood. Two signaling pathways, phosphatidylinositol 3‐kinase (PI3K)/Akt to target of rapamycin (TOR) and... more
Skeletal muscle cells are hypertrophied by mechanical stresses, but the underlying molecular mechanisms are not fully understood. Two signaling pathways, phosphatidylinositol 3‐kinase (PI3K)/Akt to target of rapamycin (TOR) and extracellular signal–regulated kinase kinase (MEK) to extracellular signal–regulated kinase (ERK), have been proposed to be involved in muscle hypertrophy. In this study we examined the involvement of these pathways in primary cultures of chick skeletal myotubes subjected to passive cyclic stretching for 72 hours, a time that was sufficient to induce significant hypertrophy in our preparations. Hypertrophy was largely suppressed by wortmannin or rapamycin, inhibitors of PI3K or mTOR, respectively. Furthermore, phosphorylation of Akt was enhanced by stretching and suppressed by wortmannin. The MEK inhibitor, U0126, exerted a minimal influence on stretch‐induced hypertrophy. We found that cyclic stretching of myotubes activates the PI3K/Akt/TOR pathway, resulting in muscle hypertrophy. The MEK/ERK pathway may contribute negatively to spontaneous hypertrophy. Muscle Nerve, 2010
Research Interests: Biology, Myogenesis, Cell Biology, Medicine, Western blotting, and 10 moreSignal Transduction, Animals, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, Hypertrophy, Protein kinase B, Muscle hypertrophy, Muscle Stretching Exercises/*methods, Chick embryo, Medical and Health Sciences, and Muscle fibers skeletal
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Research Interests: Endocrinology, Long Term Potentiation, Neuropharmacology, Medicine, Internal Medicine, and 15 moreFemale, Animals, Male, Neuronal Plasticity, Amygdala, Phenols, Neurosciences, Bicuculline, Glutamate decarboxylase, Muscimol, Basolateral Amygdala, Dopamine antagonists, dopaminergic, Attention deficit disorder with hyperactivity, and Pharmacology and pharmaceutical sciences
Research Interests: Electrophysiology, Biology, Cell Biology, Multidisciplinary, Ion Channels, and 15 moreBiological Sciences, Phylogeny, Escherichia coli, Animals, Chlamydomonas, Methionine, Glycine, Amino Acid Sequence, Chloroplast, Chlorophyta, Chlamydomonas Reinhardtii, Chloroplasts, Molecular Sequence Data, Mechanosensitive Channels, and Leucine
Research Interests: Biology, Calcium, Cell Biology, Medicine, Biological Sciences, and 15 morePhylogeny, Humans, Sequence alignment, Animals, Calcium channels, Flagella, Chlamydomonas, Protozoan Proteins, Amino Acid Sequence, Intraflagellar Transport, Motor activity, Molecular Sequence Data, Psychology and Cognitive Sciences, Medical and Health Sciences, and flagellum
Ciliates and flagellates temporarily swim backwards on collision by generating a mechanoreceptor potential. Although this potential has been shown to be associated with cilia in Paramecium, the molecular entity of the mechanoreceptor has... more
Ciliates and flagellates temporarily swim backwards on collision by generating a mechanoreceptor potential. Although this potential has been shown to be associated with cilia in Paramecium, the molecular entity of the mechanoreceptor has remained unknown. Here we show that Chlamydomonas cells express TRP11, a member of the TRP (transient receptor potential) subfamily V, in the proximal region of the flagella, and that suppression of TRP11 expression results in loss of the avoiding reaction. The results indicate that Chlamydomonas flagella exhibit mechanosensitivity, despite constant motility, by localizing the mechanoreceptor in the proximal region, where active bending is restricted.