Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of antidepressant drugs on monoamines such as norepinephrine and serotonin has been described for three decades. However, more-recent research has looked beyond cell surface receptors to transductional cascades and gene expression. Antidepressant drug therapies seem to share several mechanisms involved in either activating the adenylyl cyclase-protein kinase A cascade or inhibiting the phospholipase C-protein kinase C mechanisms. These effects, ultimately, combine to regulate the expression of target genes. Several specific genes are known to be activated or inhibited by antidepressant therapies. Steady-state levels of mRNA for glucocorticoid and mineralocorticoid receptors, brain-derived neurotrophic factor and its receptor trkB, and preproenkephalin are enhanced, whereas those for corticotropin-releasing hormone, c-fos,N-methyl-D-aspartate receptor subunits, and nerve-growth factor 1A are reduced. New molecular genetic methods for identifying differentially expressed genes will aid in the development of targets for wholly new generations of antidepressant drug therapies.
...
PMID:Intracellular mechanisms of antidepressant drug action. 1103 41

As a testable heuristic, the concept of stress response and adaptation is highly appealing, and the support for the concept is strong. This explanatory model of depression may account for hitherto apparently discordant facts--contradictory symptoms, antidepressant drugs that act on differing systems, facilitation of antidepressant response by augmentation, and response to psychotherapy and pharmacotherapy. This article has focused narrowly on specific cellular elements of the stress-adaptational mechanisms, including the AC-PKA and PLC-PKC transductional cascades, together with specific response elements, such as the HPA axis, BDNF, and NMDA receptors; however, other important mechanisms, including specific receptor subtypes (e.g., 5-HT1A and NE alpha 2), transmitter systems (e.g., acetylcholine and depamine), and hormones (e.g., thyroid and growth hormones and prolactin), which may be important, have not been discussed. As the complex interactions of these systems gradually yield to investigation, not only will new treatments be developed, but better matching of treatment to patient may become an achievable goal.
...
PMID:Cellular mechanisms in the vulnerability to depression and response to antidepressants. 1114 43

A fundamental difference between short-term and long-term forms of synaptic plasticity is the dependence on transcription and translation of new genes. Using organotypic cultures of hippocampal slices, we have investigated whether the modulation of synapses by brain-derived neurotrophic factor (BDNF) also requires protein synthesis. Long-term treatment of hippocampal slice cultures with BDNF increased the number of docked vesicles, but not that of reserve pool vesicles, at CA1 excitatory synapses. BDNF also increased the levels of the vesicle proteins synaptophysin, synaptobrevin, and synaptotagmin, without affecting the presynaptic membrane proteins syntaxin and SNAP-25, or the vesicle-binding protein synapsin-I. The increase in synaptophysin and synaptobrevin expression was moderate (2-fold) and occurred within 6 h after BDNF application. In contrast, synaptotagmin expression took 24 h to reach maximum levels (5-fold). The delayed increase in synaptotagmin was blocked by protein synthesis inhibitors, while the early increase in synaptophysin and synaptobrevin was not. Moreover, the BDNF-induced increase of synaptotagmin was blocked by inhibiting the cAMP/protein kinase A (PKA) pathway. However, BDNF did not activate PKA, and application of a PKA activator did not mimic the BDNF effect. Taken together, these results suggest a novel, protein synthesis-dependent form of BDNF modulation that requires cAMP gating.
...
PMID:Protein synthesis-dependent and -independent regulation of hippocampal synapses by brain-derived neurotrophic factor. 1148 92

The present brief review was discussed about the intracellular signal transduction mediated via 5-HT and NA receptors focussing on the mechanism of antidepressants. Recent studies demonstrated that long-term antidepressant treatments resulted in activation of cAMP pathway at several levels including CREB(cAMP response element-binding protein) and BDNF(brain-derived neurotrophic factor). These pathways are elevated via 5-HT and/or NA receptors which directly couple to the cAMP system(5-HT4,6,7 receptors or beta adrenoceptors), or via receptors that lead to activation of Ca(2+)-dependent protein kinase(5-HT2 receptors or alpha 1 adrenoceptors). Such factors could be common targets for many different type of antidepressants. Elucidation of the signal transduction mediated via 5-HT and/or NA receptors, therefore, provide significant information understanding the pathophysiology of depression.
...
PMID:[Intracellular signal transduction mediated via 5-HT and NA receptors]. 1151 41

Long-lasting forms of synaptic plasticity like the late phase of LTP (L-LTP) typically require an elevation of cAMP, the recruitment of the cAMP-dependent protein kinase (PKA), and ultimately the activation of transcription and translation; some forms also require brain-derived neurotrophic factor (BDNF). Both cAMP and BDNF can activate mitogen-activated protein kinase (MAPK/ERK), which also plays a role in LTP. However, little is known about the mechanisms whereby cAMP, BDNF, and MAPK interact. We find that increases in cAMP can rapidly activate the BDNF receptor TrkB and induce BDNF-dependent long-lasting potentiation at the Schaffer collateral-CA1 synapse in hippocampus. Surprisingly, in these BDNF-dependent forms of potentiation, which are also MAPK dependent, TrkB activation is not critical for the activation of MAPK but instead appears to modulate the subcellular distribution and nuclear translocation of the activated MAPK.
...
PMID:Some forms of cAMP-mediated long-lasting potentiation are associated with release of BDNF and nuclear translocation of phospho-MAP kinase. 1160 44

The expression of neurotrophins (NTs) and related high- and low-affinity receptors was studied in surgical samples of histologically diagnosed human tumors of the lower respiratory tract. The experiment was conducted with 30 non-small cell lung cancer specimens and in eight small cell lung cancer specimens by Western blot analysis and immunohistochemistry to assess expression and distribution of NT and NT receptor proteins in tissues examined. Immunoblots of homogenates from human tumors displayed binding of anti-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3 antibodies as well as of anti-tyrosine-specific protein kinase (Trk) A, TrkB, and TrkC receptor antibodies, with similar migration characteristics than those displayed by human beta-NGF and proteins from rat brain. A specific immunoreactivity for NTs and NT receptors was demonstrated in vessel walls, stromal fibroblasts, immune cells, and sometimes within neoplastic cell bodies. Approximately 33% of bronchioloalveolar carcinomas exhibited a strong membrane NGF and TrkA immunoreactivity, whereas 46% adenocarcinomas expressed an intense TrkA immunoreactivity but a weak immunostaining for NGF within tumor cells. Moreover, squamous cell carcinomas developed an intense TrkA immunoreactivity only within stroma surrounding neoplastic cells. A faint BDNF and TrkB immunoreactivity was documented in adenocarcinomas, squamous cell carcinomas, and small cell lung cancers. NT-3 and its corresponding TrkC receptor were found in a small number of squamous cell carcinomas within large-size tumor cells. No expression of low-affinity p75 receptor protein was found in tumor cells. The detection of NTs and NT receptor proteins in tumors of the lower respiratory tract suggests that NTs may be involved in controlling growth and differentiation of human lung cancer and/or influencing tumor behavior.
...
PMID:Neurotrophins and neurotrophin receptors in human lung cancer. 1169 49

In addition to its actions on neuronal survival and differentiation, brain-derived neurotrophic factor (BDNF) has a role in the regulation of synaptic strength. Long-term potentiation, a form of synaptic plasticity, is markedly impaired in BDNF mutant mice, but the changes were restored by the re-expression of BDNF. BDNF also influences the development of patterned connections and the growth and complexity of dendrites in the cerebral cortex. These results suggest a role for BDNF in learning and memory processes, since memory acquisition is considered to involve both short-term changes in electrical properties and long-term structural alterations in synapses. Memory acquisition is associated with an increase in BDNF mRNA and TrkB receptor activation in specific brain areas. Moreover, the pharmacologic and genetic deprivation of BDNF or its receptor TrkB results in severe impairment of learning and memory in mice, rats and chicks. The effect of BDNF on learning and memory may be linked to the modulation of NMDA and non-NMDA receptor functions as well as the expression of synaptic proteins required for exocytosis. Activation of the mitogen-associated protein kinase and/or phosphatidylinositol 3-kinase signaling pathways may be involved in BDNF-dependent learning and memory formation. It is concluded that BDNF/TrkB signaling plays an important role in learning and memory.
...
PMID:Role for brain-derived neurotrophic factor in learning and memory. 1183 37

The regulation of neurotrophin (NT) secretion is critical for many aspects of NT-mediated neuronal plasticity. Neurons release NTs by activity-regulated secretion pathways, initiated either by neurotransmitters and/or by existing NTs by a positive-feedback mechanism. This process depends on calcium release from intracellular stores. Little is known, however, about potential pathways that down-regulate NT secretion. Here we demonstrate that nitric oxide (NO) induces a rapid down-regulation of brain-derived neurotrophic factor (BDNF) secretion in cultured hippocampal neurons. Similar effects occur by activating a downstream target of intracellular NO, the soluble guanylyl cyclase, or by increasing the levels of its product, cGMP. Furthermore, down-regulation of BDNF secretion is mediated by cGMP-activated protein kinase G, which prevents calcium release from inositol 1,4,5-trisphosphate-sensitive stores. Our data indicate that the NO/cGMP/protein kinase G pathway represents a signaling mechanism by which neurons can rapidly down-regulate BDNF secretion and suggest that, in hippocampal neurons, NT secretion is finely tuned by both stimulatory and inhibitory signals.
...
PMID:Nitric oxide down-regulates brain-derived neurotrophic factor secretion in cultured hippocampal neurons. 1186 12

Pathfinding by growing axons in the developing nervous system may be guided by gradients of extracellular guidance factors. Analogous to the process of chemotaxis in microorganisms, we found that axonal growth cones of cultured Xenopus spinal neurons exhibit adaptation during chemotactic migration, undergoing consecutive phases of desensitization and resensitization in the presence of increasing basal concentrations of the guidance factor netrin-1 or brain-derived neurotrophic factor. The desensitization is specific to the guidance factor and is accompanied by a reduction of Ca2+ signalling, whereas resensitization requires activation of mitogen-associated protein kinase and local protein synthesis. Such adaptive behaviour allows the growth cone to re-adjust its sensitivity over a wide range of concentrations of the guidance factor, an essential feature for long-range chemotaxis.
...
PMID:Adaptation in the chemotactic guidance of nerve growth cones. 1198 20

Growing axons during development are guided to their targets by the activity of their growth cones. Growth cones integrate positive and negative guidance cues in deciding the direction in which to extend. We demonstrated previously that treatment of embryonic retinal ganglion cells with brain-derived neurotrophic factor (BDNF) protects their growth cones from collapse induced by nitric oxide (NO). BDNF stabilizes growth-cone actin filaments against NO-induced depolymerization. In the present study, we examined the signaling mechanism involved in BDNF-mediated protection. We found that BDNF causes transient activation of protein kinase A (PKA) during the first 5 min of treatment. Treatment with PKA inhibitors before or in conjunction with BDNF treatment blocked the protective effects of BDNF. The effects of BDNF, however, were not blocked when addition of PKA inhibitors was delayed as little as 15 min after BDNF treatment. When cultures raised overnight in BDNF were treated with PKA inhibitors, BDNF-mediated protection did not end, demonstrating that the maintenance of the protective effects of BDNF is independent of PKA activity. The BDNF-induced activation of PKA was required for BDNF-mediated stabilization of growth-cone actin filaments against depolymerization by cytochalasin D. Finally, the initiation and maintenance of the protective effects of BDNF required protein synthesis. Collectively, these data demonstrate that PKA signaling is required only for an early phase of BDNF-mediated protection from NO-induced growth-cone collapse.
...
PMID:Transient PKA activity is required for initiation but not maintenance of BDNF-mediated protection from nitric oxide-induced growth-cone collapse. 1207 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---