Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spatiotemporally regulated cell proliferation and differentiation are crucial for the successful completion of morphogenesis of the vertebrate secondary palate. An understanding of the mechanisms by which these cellular phenomena are regulated during palate development involves the identification of the various signal transduction pathways. In the present study, the presence and activation of mitogen-activated protein (MAP) kinases were investigated during the development of quail secondary palate. The palatal shelves were dissected on days 5-9 of incubation, homogenized, and centrifuged, after which the samples were separated by anion exchange fast protein liquid chromatography. The fractions were analyzed for myelin basic protein (MBP) phosphorylation. In addition, primary cultures of quail palate mesenchymal cells (QPMCs) were treated with epidermal growth factor (EGF) and prepared for MBP phosphorylation assays. A temporally regulated pattern of phosphotransferase activity, characterized by a three-fold increase in phosphotransferase activity toward MBP between days 5 and 8 of incubation, was observed during quail palate development. Western blotting, using MAP kinase antibodies, demonstrated the presence of a 42-kDa isoform between days 5 and 9 of incubation, during which the level of protein remained constant. Antityrosine immunoblotting with 4G10 also detected a 42-kDa protein. Phosphotransferase assays, using either a MAP kinase-specific substrate peptide (S5) or a protein kinase C inhibitor (R3), further confirmed the presence of a MAP kinase in the developing palate of quail. Because diverse biological processes occur concurrently during in vivo palate morphogenesis, the involvement of MAP kinase was explored further in primary cell culture. The data showed that EGF stimulated proliferation and activated 42-kDa MAP kinase in QPMCs. It is suggested that MAP kinase cascade may be involved in growth factor-regulated cell proliferation during morphogenesis of quail secondary palate.
Anat Rec 1998 10
PMID:In vivo and in vitro assessment of mitogen activated protein kinase involvement during quail secondary palate formation. 977 74

Previous studies demonstrated that corneal epithelial cells isolated without basal lamina respond to extracellular matrix (ECM) in an actin dependent manner; the basal cell surface flattens and the actin cortical mat reorganizes. We hypothesize that the actin reorganization is initiated by intracellular signaling mechanisms that includes tyrosine phoshporylation and activation of the Rho, MAP kinase, and PI3 kinase signal transduction pathways. Our goals were to develop a morphological assay to test this hypothesis by answering the following questions: 1) Do the actin bundle formations in the cortical mat have the same configuration in response to different ECM molecules? 2) What is the minimum time ECM molecules need to be in contact with the tissue for the actin to reorganize? 3) Will blocking tyrosine phosphorylation inhibit reorganization of the actin? 4) Are known signal transduction proteins phosphorylated in response to soluble matrix molecules? The actin cortical mat demonstrated distinct bundle configurations in the presence of different ECM molecules. Soluble fibronectin accumulated at the basal cell surfaces 75-fold over 30 min in a clustered pattern. The cells need contact with ECM for a minimum of 10 min to reform the actin bundles at 2 hr. In contrast, two substances that bind to heptahelical receptors to stimulate the Rho pathway, bombesin and lysophosphatidic acid, reorganized the actin bundles in 15-30 min. Focal adhesion kinase, p190 Rho-GAP, tensin, and paxillin were tyrosine phosphorylated in response to soluble fibronectin, type I collagen, or laminin 1. Erk-1, erk-2, and PI3 kinase were activated after 1 hr stimulation by type I collagen. Herbimycin A blocked actin reorganization induced by ECM molecules. In conclusion, we have developed two morphological assays to examine the response of corneal epithelial cells to ECM molecules. In addition, actin bundle reorganization involved tyrosine phosphorylation, MAP kinase, and PI3 kinase activation.
Anat Rec 1999 03
PMID:ECM-stimulated actin bundle formation in embryonic corneal epithelia is tyrosine phosphorylation dependent. 1009 66

Toxic effects of cocaine on the heart muscle have been known for many years. Cardiovascular complications related to cocaine abuse include myocardial ischemia and infarction, inflammation, and disease of the heart muscle, rhythm disturbances, and sudden cardiac death. Cocaine toxicity-related cardiac morbidity and mortality are often due to several interacting mechanisms. Cocaine also has a potent pharmacological effect, indirectly stimulating the sympathetic nervous system, and it has a direct toxic effect on the heart. Although apoptosis (also called programmed cell death) has been shown to play an important role in the pathogenesis of several diseases in the heart, including heart failure and ischemic myocardial infarction, the role of apoptosis in the toxic effect of cocaine on the heart has not been explored. Recent studies indicated that cocaine causes apoptotic cell death in both adult and fetal heart muscles. Increased oxidative stress and reactive oxygen species, and the subsequent activation of a "stress responsive" enzyme (p38-mitogen-activated protein kinase) in the heart may play an important role in cocaine-induced apoptosis in the heart muscle. These findings suggest a new way to understand the cardiotoxic effects of cocaine, and may have potential clinical implications in the better management of cocaine-induced heart diseases. Anat Rec (New Anat): 257:208-216, 1999.
Anat Rec 1999 12 15
PMID:Cocaine and apoptosis in myocardial cells. 1062 Jul 50

Receptor tyrosine kinase (RTK) signaling is involved in multiple cell fate determination during Drosophila oogenesis. To address the problem of signaling specificity, we sought to systematically document the expression pattern of activated MAP kinase, the downstream effector of RTK signaling. We show that MAP kinase is activated in some of the cell types in which Drosophila EGF receptor signaling is known to function. MAP kinase activation is also associated with many cell migration events. Finally, MAP kinase is activated by heat stress without altering follicle cell fates. The implications of these findings are discussed.
Anat Rec A Discov Mol Cell Evol Biol 2003 May
PMID:EGF-dependent and independent activation of MAP kinase during Drosophila oogenesis. 1270 93

The present study investigated the tolerance of the isolated rat heart to ischemia-reperfusion after administration of trimetazidine (TMZ) at different experimental phases, as well as the possible involvement of p38 MAPK and JNKs in this response. Isolated rat hearts were perfused in Langendorff mode. Untreated hearts after stabilization (S) were subjected to 20 min of zero-flow global ischemia (I) and 45 min of reperfusion (R), (NORM), n = 9. TMZ (10(-5) M) was administered (in the perfusate): a) only at S phase, (TMZ-STAB), n = 8, b) only at R, (TMZ-REP), n = 8 and c) during both S and R, (TMZ-STAB+REP), n = 8. Recovery of left ventricular developed pressure at 45 min of R (Rec) was significantly higher in TMZ-STAB and TMZ-STAB+REP and LDH release was lower in TMZ-STAB+REP and TMZ-STAB than NORM, [1153.2 (121.0) and 1152.1 (86.8) vs 1573.5 (138.2), P < 0.05]. TMZ induced cardioprotection did not involve p38 MAPK and JNKs. Phospho-p38 MAPK and JNKs levels after I/R were not changed with TMZ treatment. In TMZ-REP, Rec and LDH release were similar to NORM, but the rate of functional recovery (ratio of Rec at 10 min of R to Rec) was 86.7% (13.3) for TMZ-REP vs 53.8% (7.7) for NORM, P < 0.05. This effect was associated with decreased myocardial lactate content early at reperfusion. In conclusion, preischemic administration of TMZ protects against I/R injury while TMZ given only at reperfusion accelerates recovery of function without reducing the extent of injury.
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PMID:Trimetazidine protects isolated rat hearts against ischemia-reperfusion injury in an experimental timing-dependent manner. 1561 64

One series of our research has shown an intense expression of immunoreaction for heat shock protein 25 (Hsp25) in various cellular elements in the rat temporomandibular joint (TMJ). This protein is the major substrate of mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK-2), which mediates an intracellular stress-activated signaling pathway to stimulate cytosolic actin reorganization under various stresses. The present study was undertaken to examine the localization of MAPKAPK-2 in the rat TMJ by immunocytochemical techniques. Furthermore, confocal microscopy with double staining was employed to demonstrate the colocalization of MAPKAPK-2 and Hsp25. Immunocytochemistry for MAPKAPK-2 showed an intense immunoreaction in the cytoplasm of the synovial lining cells, the endothelial cells, and the fibroblasts in the synovial membrane of the rat TMJ. Double immunostaining under a confocal microscope succeeded in demonstrating the colocalization of MAPKAPK-2 and Hsp25 immunoreactions in the cytoplasm of fibroblastic type B synoviocytes in the TMJ. On the other hand, the macrophage-like type A-cells expressed MAPKAPK-2 immunoreactions but lacked Hsp25 immunoreactivity. The cells in the articular disk and the chondrocytes in the maturative and hypertrophic layer of the mandibular cartilage also showed intense immunoreactions for MAPKAPK-2 and Hsp25. In addition to cytoplasmic localization, MAPKAPK-2 immunoreactions were found in the nucleus of some synovial lining cells, cells in the articular disk, and chondrocytes. Current observations imply the presence of the phosphorylation of Hsp25 via activated MAPKAPK-2 in the cytoplasm. MAPKAPK-2 and Hsp25 possibly participate in the induction of cytoskeletal changes to the various cellular elements in rat TMJ under normal conditions.
Anat Rec A Discov Mol Cell Evol Biol 2005 Jun
PMID:Immunocytochemical localization of MAPKAPK-2 and Hsp25 in the rat temporomandibular joint. 1579 78

The periaqueductal gray matter (PAG), the midbrain region made up of neuronal columns encircling the cerebral aqueduct, plays a key role in nociception. As the extracellular signal-regulated kinases (ERKs) 1 and 2 are activated after noxious stimulation, we analyzed the distribution of ERK-activated neurons in the PAG after visceral noxious stimulation. Ether- and urethane-anesthetized rats received an intraperitoneal injection of acetic acid or were left untreated and were perfused after 2 hr. Serial sections immunoreacted with an antibody selective for the activated ERKs. Significant ERK activation occurred only in the ether-anesthetized noxious stimulated rats. In these rats, we evaluated the number of ERK-activated neurons and their density as the ratio of the number of immunolabeled neurons to the extension of the region where they were located. ERK-activated neurons were more numerous in the lateral (LPAG) and ventrolateral (VLPAG) columns, but without significant differences. No ERK activation was seen in neurons of the most rostral PAG. The ERK-activated neurons were significantly denser at the intermediate level of the PAG. At the caudal level, they were denser in the LPAG and VLPAG columns, and in the DPAG column at the intermediate and rostral level. These findings suggest that noxious stimulation activates ERKs in neurons involved in the different functional activities related to nociception, overlapping in the PAG columns, and strengthens the role of PAG in integration.
Anat Rec A Discov Mol Cell Evol Biol 2005 May
PMID:Distribution of extracellular signal-regulated kinase 1- and 2-activated neurons in the rat periaqueductal gray matter after noxious stimulation. 1579 81

A breakthrough for studying the neuronal basis of learning emerged when invertebrates with simple nervous systems, such as the sea slug Hermissenda crassicornis, were shown to exhibit classical conditioning. Hermissenda learns to associate light with turbulence: prior to learning, naive animals move toward light (phototaxis) and contract their foot in response to turbulence; after learning, conditioned animals delay phototaxis in response to light. The photoreceptors of the eye, which receive monosynaptic inputs from statocyst hair cells, are both sensory neurons and the first site of sensory convergence. The memory of light associated with turbulence is stored as changes in intrinsic and synaptic currents in these photoreceptors. The subcellular mechanisms producing these changes include activation of protein kinase C and MAP kinase, which act as coincidence detectors because they are activated by convergent signaling pathways. Pathways of interneurons and motorneurons, where additional changes in excitability and synaptic connections are found, contribute to delayed phototaxis. Bursting activity recorded at several points suggest the existence of small networks that produce complex spatiotemporal firing patterns. Thus, the change in behavior may be produced by a nonlinear transformation of spatiotemporal firing patterns caused by plasticity of synaptic and intrinsic channels. The change in currents and the activation of PKC and MAPK produced by associative learning are similar to those observed in hippocampal and cerebellar neurons after rabbit classical conditioning, suggesting that these represent general mechanisms of memory storage. Thus, the knowledge gained from further study of Hermissenda will continue to illuminate mechanisms of mammalian learning.
Anat Rec B New Anat 2006 Jan
PMID:Subcellular, cellular, and circuit mechanisms underlying classical conditioning in Hermissenda crassicornis. 1643 55

Achondroplasia, the most common short-limbed dwarfism in humans, results from a single nucleotide substitution in the gene for fibroblast growth factor receptor 3 (FGFR3). FGFR3 regulates bone growth in part via the mitogen-activated protein kinase pathway (MAPK). To examine the role of this pathway in chondrocyte differentiation, a transgenic mouse was generated that expresses a constitutively active mutant of MEK1 in chondrocytes and exhibits dwarfing characteristics typical of human achondroplasia, i.e., shortened axial and appendicular skeletons, mid-facial hypoplasia, and dome-shaped cranium. In this study, cephalometrics of the MEK1 mutant skulls were assessed to determine if the MEK1 mice are a good model of achondroplasia. Skull length, arc of the cranial vault, and area, maximum and minimum diameters of the brain case were measured on digitized radiographs of skulls of MEK1 and control mice. Cranial base and nasal bone length and foramen magnum diameter were measured on midsagittal micro-CT sections. Data were normalized by dividing by the cube root of each animal's weight. Transgenic mice exhibited a domed skull, deficient midface, and (relatively) prognathic mandible and had a shorter cranial base and nasal bone than the wild-type. Skull length was significantly less in transgenic mice, but cranial arc was significantly greater. The brain case was larger and more circular and minimum diameter of the brain case was significantly greater in transgenic mice. The foramen magnum was displaced anteriorly but not narrowed. MEK1 mouse cephalometrics confirm these mice as a model for achondroplasia, demonstrating that the MAP kinase signaling pathway is involved in FGF signaling in skeletal development.
Anat Rec A Discov Mol Cell Evol Biol 2006 Mar
PMID:Aspects of achondroplasia in the skulls of dwarf transgenic mice: a cephalometric study. 1646 80

Cochlear implantation trauma and noise-induced hearing loss both involve a physical disruption of the organ of Corti and may involve several mechanisms of cell death at the molecular level, i.e., necrosis, necrosis-like programmed cell death (PCD; type 2 PCD), and apoptosis (type 1 PCD). This article reviews several promising therapeutic strategies that are currently being developed. One of these promising new strategies involves the use of a highly effective peptide inhibitor of the c-Jun N-terminal kinase cell death signal cascade (i.e., D-JNKI-1) to prevent apoptosis of injured auditory hair cells. Our recent studies showed prevention of cochlear implantation-induced hearing loss by infusing this peptide into the cochlea of guinea pigs. Another otoprotective therapy under investigation is the application of mild hypothermia to protect the cochlea from the development of a hearing loss that follows exposure to a physical trauma, e.g., electrode array insertional trauma. These forward-looking strategies have the potential of improving hearing outcomes after cochlear implantation and providing novel means of otoprotection from noise-induced trauma.
Anat Rec A Discov Mol Cell Evol Biol 2006 Apr
PMID:Cochlear implantation trauma and noise-induced hearing loss: Apoptosis and therapeutic strategies. 1655 May 92


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