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1.
Immune Network ; : e14-2018.
Article in English | WPRIM | ID: wpr-740198

ABSTRACT

T lymphocytes rely on several metabolic processes to produce the high amounts of energy and metabolites needed to drive clonal expansion and the development of effector functions. However, many of these pathways result in the production of reactive oxygen species (ROS), which have canonically been thought of as cytotoxic agents due to their ability to damage DNA and other subcellular structures. Interestingly, ROS has recently emerged as a critical second messenger for T cell receptor signaling and T cell activation, but the sensitivity of different T cell subsets to ROS varies. Therefore, the tight regulation of ROS production by cellular antioxidant pathways is critical to maintaining proper signal transduction without compromising the integrity of the cell. This review intends to detail the common metabolic sources of intracellular ROS and the mechanisms by which ROS contributes to the development of T cell-mediated immunity. The regulation of ROS levels by the glutathione pathway and the Nrf2-Keap1-Cul3 trimeric complex will be discussed. Finally, T cell-mediated autoimmune diseases exacerbated by defects in ROS regulation will be further examined in order to identify potential therapeutic interventions for these disorders.


Subject(s)
Antioxidants , Autoimmune Diseases , Autoimmunity , Cytotoxins , DNA , Glutathione , Immunity, Cellular , Metabolism , Reactive Oxygen Species , Receptors, Antigen, T-Cell , Second Messenger Systems , Signal Transduction , T-Lymphocyte Subsets , T-Lymphocytes
2.
Article in English | WPRIM | ID: wpr-656361

ABSTRACT

OBJECTIVES: Estrogen is an important hormone for cell growth, development, and differentiation by transcriptional regulation and modulation of intracellular signaling via second messengers. The reduction in the estrogen level after ovariectomy may lead to cognitive impairments associated with morphological changes in areas of the brain mediate memory. The aim of the present study was to find out the effect of tasks on the cognitive function after ovariectomy in rats. METHODS: The animals used in the experiment were 50 Sprague-Dawley female rats. This study applied a hippocampus-independent task (wheel running) and a hippocampus-dependent task (Morris water maze) after ovariectomy in rats and measured the cognitive performance (object-recognition and object-location test) and growth-associated protein 43 (GAP-43) and neurotrophin 3 (NT-3) expression in the hippocampus, which is an important center for memory and learning. RESULTS: There were meaningful differences between the hippocampus-independent and hippocampus-dependent task groups for the object-location test and GAP-43 and NT-3 expression in the hippocampus, but not the object-recognition test. However, the hippocampus-independent task group showed a significant improvement in the object-recognition test, compared to the control group. CONCLUSION: These results suggest that hippocampus-dependent task training after ovariectomy enhances the hippocampus-related memory and cognitive function that are associated with morphological and functional changes in the cells of the hippocampus.


Subject(s)
Animals , Brain , Cognition Disorders , Cognition , Estrogens , Female , GAP-43 Protein , Hippocampus , Humans , Learning , Memory , Neurotrophin 3 , Ovariectomy , Rats , Rats, Sprague-Dawley , Second Messenger Systems , Water
3.
Article in English | WPRIM | ID: wpr-764776

ABSTRACT

Calcium has versatile roles in diverse physiological functions. Among these functions, intracellular Ca²⁺ plays a key role during the secretion of salivary glands. In this review, we introduce the diverse cellular components involved in the saliva secretion and related dynamic intracellular Ca²⁺ signals. Calcium acts as a critical second messenger for channel activation, protein translocation, and volume regulation, which are essential events for achieving the salivary secretion. In the secretory process, Ca²⁺ activates K⁺ and Cl⁻ channels to transport water and electrolyte constituting whole saliva. We also focus on the Ca²⁺ signals from intracellular stores with discussion about detailed molecular mechanism underlying the generation of characteristic Ca²⁺ patterns. In particular, inositol triphosphate signal is a main trigger for inducing Ca²⁺ signals required for the salivary gland functions. The biphasic response of inositol triphosphate receptor and Ca²⁺ pumps generate a self-limiting pattern of Ca²⁺ efflux, resulting in Ca²⁺ oscillations. The regenerative Ca²⁺ oscillations have been detected in salivary gland cells, but the exact mechanism and function of the signals need to be elucidated. In future, we expect that further investigations will be performed toward better understanding of the spatiotemporal role of Ca²⁺ signals in regulating salivary secretion.


Subject(s)
Calcium Signaling , Calcium , Chloride Channels , Inositol , Inositol 1,4,5-Trisphosphate Receptors , Protein Transport , Saliva , Salivary Glands , Salivation , Second Messenger Systems , Secretory Pathway , Water
4.
Article in English | WPRIM | ID: wpr-165936

ABSTRACT

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P₁₋₅. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn’s disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications.


Subject(s)
Acute Kidney Injury , Animals , Clone Cells , Cloning, Organism , Colitis, Ulcerative , Dermatomyositis , Drug Discovery , Fingolimod Hydrochloride , Graft Rejection , In Vitro Techniques , Liver Failure , Mice , Multiple Sclerosis , Polymyositis , Psoriasis , Receptors, Lysosphingolipid , Second Messenger Systems , Sphingosine , Stroke
5.
Experimental Neurobiology ; : 227-239, 2017.
Article in English | WPRIM | ID: wpr-22192

ABSTRACT

Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i.c.v.) administration of ex-4 or ex9-39. Oxygen-glucose deprivation was also induced in primary neurons, bEnd.3 cells, and BV-2. Ischemia-reperfusion injury reduced expression of GLP-1R. Additionally, higher oxidative stress in SOD2 KO mice decreased expression of GLP-1R. Downregulation of GLP-1R by ischemic injury was 70% restored by GLP-1R agonist, ex-4, which resulted in significant reduction of infarct volume. Levels of intracellular cyclic AMP, a second messenger of GLP-1R, were also increased by 2.7-fold as a result of high GLP-1R expression. Moreover, our results showed that ex-4 attenuated pro-inflammatory cyclooxygenase-2 (COX-2) and prostaglandin E₂ after MCAO. C-Jun NH₂ terminal kinase (JNK) signaling, which stimulates activation of COX-2, was 36% inhibited by i.c.v. injection of ex-4 at 24 h. Islet-brain 1 (IB1), a scaffold regulator of JNK, was 1.7-fold increased by ex-4. GLP-1R activation by ex-4 resulted in reduction of COX-2 through increasing IB1 expression, resulting in anti-inflammatory neuroprotection during stroke. Our study suggests that the anti-inflammatory action of GLP-1 could be used as a new strategy for the treatment of neuroinflammation after stroke accompanied by hyperglycemia.


Subject(s)
Animals , Brain Ischemia , Cyclic AMP , Cyclooxygenase 2 , Diabetes Mellitus, Type 2 , Down-Regulation , Glucagon , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Hyperglycemia , Infarction, Middle Cerebral Artery , Insulin , Mice , Neurons , Neuroprotection , Neuroprotective Agents , Oxidative Stress , Phosphotransferases , Rats , Reperfusion Injury , Second Messenger Systems , Stroke
6.
Article in English | WPRIM | ID: wpr-51973

ABSTRACT

Estrogen - the female sexual hormone playing the most important role - plays a physiologically significant role, not only regulating in cell signals with second messenger but also being active in regulating transcription. Estrogen receptor (ER) which is a protein accepting estrogen not only play the role of a transcription factor combining with other genes to regulate their activity like other nuclear receptors but also performs external activities, combining with DNA, etc. G-protein coupled ER (GPER) that has been recently discovered exists as 7-membrane and has non-genomic (rapid) signaling. These functions, however, are not extensively addressed. This paper discusses the roles of GPER and its physiological mechanism.


Subject(s)
DNA , Estradiol , Estrogens , Female , Genomics , GTP-Binding Proteins , Humans , Receptors, Cytoplasmic and Nuclear , Second Messenger Systems , Transcription Factors , Women's Health
7.
Indian J Hum Genet ; 2014 Jan-Mar ;20 (1): 4-9
Article in English | IMSEAR | ID: sea-156627

ABSTRACT

Oral cancers have been one of the leading causes of deaths particularly in the developing countries. Prime reason for this high mortality and morbidity is attributed to the delay in diagnosis and prompt treatment. Relentless research in the field of oncology has led to the advent of novel procedures for the early detection of oral cancers. Molecular biology is highly promising in this regard. It is a procedure that detects alterations at a molecular level much before they are seen under a microscope and much before clinical changes occur. Molecular studies serve as the basis by which we will eventually be able not only to augment clinical assessment and classification of oral lesions but also predict malignant potential of oral lesions, thus reducing the incidence and increasing the scope for early diagnosis and treatment of oral cancers. However, making such sophisticated tools available for the common man in developing countries is one of the most important challenges faced today.


Subject(s)
Cytogenetics , Genes, Tumor Suppressor/genetics , Humans , Mouth Neoplasms/genetics , Oncogenes , Second Messenger Systems/genetics , Transcription, Genetic
8.
Protein & Cell ; (12): 117-129, 2013.
Article in English | WPRIM | ID: wpr-757835

ABSTRACT

Initial skirmishes between the host and pathogen result in spillage of the contents of the bacterial cell. Amongst the spillage, the secondary messenger molecule, cyclic dimeric guanosine monophosphate (c di-GMP), was recently shown to be bound by stimulator of interferon genes (STING). Binding of c di-GMP by STING activates the Tank Binding Kinase (TBK1) mediated signaling cascades that galvanize the body's defenses for elimination of the pathogen. In addition to c di-GMP, STING has also been shown to function in innate immune responses against pathogen associated molecular patterns (PAMPs) originating from the DNA or RNA of pathogens. The pivotal role of STING in host defense is exemplified by the fact that STING(-/-) mice die upon infection by HSV-1. Thus, STING plays an essential role in innate immune responses against pathogens. This opens up an exciting possibility of targeting STING for development of adjuvant therapies to boost the immune defenses against invading microbes. Similarly, STING could be targeted for mitigating the inflammatory responses augmented by the innate immune system. This review summarizes and updates our current understanding of the role of STING in innate immune responses and discusses the future challenges in delineating the mechanism of STING-mediated responses.


Subject(s)
Animals , Cyclic GMP , Physiology , Dimerization , Herpes Simplex , Allergy and Immunology , Pathology , Humans , Immunity, Innate , Membrane Proteins , Chemistry , Genetics , Metabolism , Protein Binding , RNA, Viral , Metabolism , STAT6 Transcription Factor , Metabolism , Second Messenger Systems
9.
Article in English | WPRIM | ID: wpr-728179

ABSTRACT

Understanding the cellular and molecular mechanisms involved in the development and progression of pulmonary hypertension (PH) remains imperative if we are to successfully improve the quality of life and life span of patients with the disease. A whole plethora of mechanisms are associated with the development and progression of PH. Such complexity makes it difficult to isolate one particular pathway to target clinically. Changes in intracellular free calcium concentration, the most common intracellular second messenger, can have significant impact in defining the pathogenic mechanisms leading to its development and persistence. Signaling pathways leading to the elevation of [Ca2+]cyt contribute to pulmonary vasoconstriction, excessive proliferation of smooth muscle cells and ultimately pulmonary vascular remodeling. This current review serves to summarize the some of the most recent advances in the regulation of calcium during pulmonary hypertension.


Subject(s)
Calcium , Humans , Hydrogen-Ion Concentration , Hypertension, Pulmonary , Myocytes, Smooth Muscle , Quality of Life , Second Messenger Systems , Vasoconstriction
10.
Hanyang Medical Reviews ; : 77-82, 2013.
Article in Korean | WPRIM | ID: wpr-86608

ABSTRACT

Reactive oxygen species (ROS) are the chemical species that includes the superoxide anion, hydrogen peroxide and hydrogen radical. These ROS are simply thought as a group of molecules harmful to cells because they oxidize proteins, lipids and DNA, and they mediate cell death including apoptosis or necrosis. On the other hand, ROS have been shown to act as essential intracellular second messengers for certain cytokines and growth factors. Although the importance of ROS in the execution of cell death is controversial, ROS are likely to be involved in the signal transduction mechanism for cell death as signaling intermediates in death receptor initiated signaling pathways, specifically in the tumor necrosis factor alpha-tumor necrosis factor receptor 1 (TNFalpha-TNFR1) pathway. In this review, using TNFalpha-TNFR as the model system, we attempt to address the involvement of intracellular ROS in TNFalpha induced cell death, including apoptosis, necrosis and an alternative form of programmed cell death, necroptosis.


Subject(s)
Apoptosis , Cell Death , Cytokines , DNA , Hand , Hydrogen , Hydrogen Peroxide , Intercellular Signaling Peptides and Proteins , Necrosis , Proteins , Reactive Oxygen Species , Second Messenger Systems , Signal Transduction , Superoxides , Tumor Necrosis Factor-alpha
11.
Article in English | WPRIM | ID: wpr-128752

ABSTRACT

A growing body of evidence suggests that hyperglycemia-induced oxidative stress plays an important role in diabetic complications, especially beta-cell dysfunction and failure. Under physiological conditions, reactive oxygen species serve as second messengers that facilitate signal transduction and gene expression in pancreatic beta-cells. However, under pathological conditions, an imbalance in redox homeostasis leads to aberrant tissue damage and beta-cell death due to a lack of antioxidant defense systems. Taking into account the vulnerability of islets to oxidative damage, induction of endogenous antioxidant enzymes or exogenous antioxidant administration has been proposed as a way to protect beta-cells against diabetic insults. Here, we consider recent insights into how the redox response becomes deregulated under diabetic conditions, as well as the therapeutic benefits of antioxidants, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with beta-cell failure.


Subject(s)
Antioxidants , Choristoma , Diabetes Complications , Gene Expression , Homeostasis , Nitric Oxide , Oxidation-Reduction , Oxidative Stress , Reactive Nitrogen Species , Reactive Oxygen Species , Second Messenger Systems , Signal Transduction , Superoxide Dismutase
12.
Protein & Cell ; (12): 535-544, 2012.
Article in English | WPRIM | ID: wpr-757241

ABSTRACT

Curcumin, an active ingredient of dietary spice used in curry, has been shown to exhibit anti-oxidant, anti-inflammatory and anti-proliferative properties. Using EB directed differentiation protocol of H-9 human embryonic stem (ES) cells; we evaluated the effect of curcumin (0-20 μmol/L) in enhancing such differentiation. Our results using real time PCR, western blotting and immunostaining demonstrated that curcumin significantly increased the gene expression and protein levels of cardiac specific transcription factor NKx2.5, cardiac troponin I, myosin heavy chain, and endothelial nitric oxide synthase during ES cell differentiation. Furthermore, an NO donor enhanced the curcumin-mediated induction of NKx2.5 and other cardiac specific proteins. Incubation of cells with curcumin led to a dose dependent increase in intracellular nitrite to the same extent as giving an authentic NO donor. Functional assay for second messenger(s) cyclic AMP (cAMP) and cyclic GMP (cGMP) revealed that continuous presence of curcumin in differentiated cells induced a decrease in the baseline levels of cAMP but it significantly elevated baseline contents of cGMP. Curcumin addition to a cell free assay significantly suppressed cAMP and cGMP degradation in the extracts while long term treatment of intact cells with curcumin increased the rates of cAMP and cGMP degradation suggesting that this might be due to direct suppression of some cyclic nucleotide-degrading enzyme (phosphodiesterase) by curcumin. These studies demonstrate that polyphenol curcumin may be involved in differentiation of ES cells partly due to manipulation of nitric oxide signaling.


Subject(s)
Animals , Antioxidants , Pharmacology , Cell Differentiation , Cells, Cultured , Curcumin , Pharmacology , Cyclic GMP , Metabolism , Embryoid Bodies , Metabolism , Physiology , Enzyme Activators , Pharmacology , Gene Expression , Guanylate Cyclase , Genetics , Metabolism , Homeodomain Proteins , Genetics , Metabolism , Humans , Mice , Myosin Heavy Chains , Genetics , Metabolism , Nitric Oxide , Metabolism , Nitric Oxide Donors , Pharmacology , Nitric Oxide Synthase Type III , Genetics , Metabolism , Nitroso Compounds , Pharmacology , Pyrazoles , Pharmacology , Pyridines , Pharmacology , Second Messenger Systems , Transcription Factors , Genetics , Metabolism , Troponin , Genetics , Metabolism , Tumor Suppressor Protein p53 , Metabolism
13.
Journal of Ophthalmic and Vision Research. 2012; 7 (1): 107-108
in English | IMEMR | ID: emr-163690
14.
Acta Pharmaceutica Sinica ; (12): 307-312, 2012.
Article in Chinese | WPRIM | ID: wpr-323042

ABSTRACT

Cyclic diguanylate (c-di-GMP) is a ubiquitous second messenger present in a wide variety of bacteria, which is responsible for cell differentiation, biofilm formation, pathogenic factor generation, and so on. The level of c-di-GMP in bacteria is regulated by two opposing active domains, diguanylate cyclase (DGC) and phosphodiesterase (PDE), which are present in the same bifunctional protein, and in charge of the synthesis and the degradation of c-di-GMP, respectively. The target of c-di-GMP in the bacterial cell consists of PilZ domain and GEMM riboswitch, the only riboswitch that involved in signal transduction. This article gives an overview of c-di-GMP, focusing on its metabolic pathway, regulatory mechanism, biological function of c-di-GMP, and the synthesis of c-di-GMP analogues and their biological activity.


Subject(s)
Bacteria , Metabolism , Cyclic GMP , Metabolism , Escherichia coli Proteins , Chemistry , Metabolism , Phosphoric Diester Hydrolases , Chemistry , Metabolism , Phosphorus-Oxygen Lyases , Chemistry , Metabolism , Riboswitch , Second Messenger Systems , Signal Transduction
15.
Article in English | WPRIM | ID: wpr-210391

ABSTRACT

Glycosphingolipids (GSLs) are present in all mammalian cell plasma membranes and intracellular membrane structures. They are especially concentrated in plasma membrane lipid domains that are specialized for cell signaling. Plasma membranes have typical structures called rafts and caveola domain structures, with large amounts of sphingolipids, cholesterol, and sphingomyelin. GSLs are usually observed in many organs ubiquitously. However, GSLs, including over 400 derivatives, participate in diverse cellular functions. Several studies indicate that GSLs might have an effect on signal transduction related to insulin receptors and epidermal growth factor receptors. GSLs may modulate immune responses by transmitting signals from the exterior to the interior of the cell. Guillain-Barre syndrome is one of the autoimmune disorders characterized by symmetrical weakness in the muscles of the legs. The targets of the immune response are thought to be gangliosides, which are one group of GSLs. Other GSLs may serve as second messengers in several signaling pathways that are important to cell survival or programmed cell death. In the search for clear evidence that GSLs may play critical roles in various biological functions, many researchers have made genetically engineered mice. Before the era of gene manipulation, spontaneous animal models or chemical-induced disease models were used.


Subject(s)
Animals , Caveolae , Cell Death , Cell Membrane , Cell Survival , Cholesterol , Diabetes Mellitus , Gangliosides , Glycosphingolipids , Guillain-Barre Syndrome , Intracellular Membranes , Leg , Mice , Models, Animal , Muscles , ErbB Receptors , Receptor, Insulin , Second Messenger Systems , Signal Transduction , Sphingolipids
16.
Chonnam Medical Journal ; : 27-30, 2011.
Article in English | WPRIM | ID: wpr-170946

ABSTRACT

Sphingosine-1-phosphate (S1P) is emerging as a new class of second messenger involved in cellular proliferation, differentiation, and apoptosis and is implicated in diverse physiological functions. Despite many studies on the biological functions of S1P, however, little is known about its role in neuronal differentiation. By use of reverse transcription-polymerase chain reaction and immunostaining, this study aimed to explore whether S1P can differentiate neuroblastoma cells into neural cells. After incubation with 1 uM or 10 uM S1P, the number of neurite-bearing cells increased. Furthermore, the neuroblastoma cells revealed immunoreactivity for neural-specific markers such as GAP43, NFH, and SYP by immunostaining. The expression of NFH, MAP2, SYP, NeuroD1, and SYT mRNA, which is specific for neurons, was increased as shown by RT-PCR studies. The results of this study suggest that that S1P can induce neuronal differentiation and may be a good candidate for the treatment of neurodegenerative diseases.


Subject(s)
Apoptosis , Cell Differentiation , Cell Proliferation , Lysophospholipids , Neurites , Neuroblastoma , Neurodegenerative Diseases , Neurons , RNA, Messenger , Second Messenger Systems , Sphingosine
17.
Hanyang Medical Reviews ; : 123-133, 2011.
Article in Korean | WPRIM | ID: wpr-19501

ABSTRACT

The sigma-1 receptor has recently been implicated in a myriad of cellular functions and biological processes. Previous studies have demonstrated that the spinal sigma-1 receptor plays a pro-nociceptive role in acute pain and that the direct activation of sigma-1 receptor enhances the nociceptive response to peripheral stimuli, which is closely associated with calcium-dependent second messenger cascades including protein kinase C (PKC). In addition, the activation of sigma-1 receptor increases PKC- and protein kinase alpha (PKA)-dependent phosphorylation of the N-Methyl- D-aspartate (NMDA) receptor in the spinal cord, which results in the potentiation of intrathecal NMDA-evoked spontaneous pain behavior. Moreover, the blockade of spinal sigma-1 receptor suppresses the development of neuropathic pain and blocks the increase of phosphorylation of extracellular signal-regulated kinase (ERK) as well as pNR1 in the spinal cord. Recently, it was also reported that spinal neurosteroids such as pregnenolone and dehydroepiandrosterone sulfate, which are recognized as endogenous ligands for sigma-1 receptor, could produce mechanical hypersensitivity via sigma-1 receptor-mediated increase of pNR1. Collectively, these findings demonstrate that the activation of spinal sigma-1 receptor or the increase of neurosteroids is closely associated with the acute pain sensation or the development of chronic pain, and imply that sigma-1 receptor can be a new potential target for the development of analgesics.


Subject(s)
Acute Pain , Analgesics , Biological Phenomena , Central Nervous System Sensitization , Chronic Pain , D-Aspartic Acid , Dehydroepiandrosterone Sulfate , Hypersensitivity , Ligands , Neuralgia , Neurotransmitter Agents , Phosphorylation , Phosphotransferases , Pregnenolone , Protein Kinase C , Protein Kinases , Receptors, sigma , Second Messenger Systems , Sensation , Spinal Cord
18.
Chonnam Medical Journal ; : 27-30, 2011.
Article in English | WPRIM | ID: wpr-788190

ABSTRACT

Sphingosine-1-phosphate (S1P) is emerging as a new class of second messenger involved in cellular proliferation, differentiation, and apoptosis and is implicated in diverse physiological functions. Despite many studies on the biological functions of S1P, however, little is known about its role in neuronal differentiation. By use of reverse transcription-polymerase chain reaction and immunostaining, this study aimed to explore whether S1P can differentiate neuroblastoma cells into neural cells. After incubation with 1 uM or 10 uM S1P, the number of neurite-bearing cells increased. Furthermore, the neuroblastoma cells revealed immunoreactivity for neural-specific markers such as GAP43, NFH, and SYP by immunostaining. The expression of NFH, MAP2, SYP, NeuroD1, and SYT mRNA, which is specific for neurons, was increased as shown by RT-PCR studies. The results of this study suggest that that S1P can induce neuronal differentiation and may be a good candidate for the treatment of neurodegenerative diseases.


Subject(s)
Apoptosis , Cell Differentiation , Cell Proliferation , Lysophospholipids , Neurites , Neuroblastoma , Neurodegenerative Diseases , Neurons , RNA, Messenger , Second Messenger Systems , Sphingosine
19.
Article in Korean | WPRIM | ID: wpr-9937

ABSTRACT

Substantia gelatinosa (SG) neurons receive synaptic inputs from primary afferent Adelta- and C-fibers, where nociceptive information is integrated and modulated by numerous neurotransmitters or neuromodulators. A number of studies were dedicated to the molecular mechanism underlying the modulation of excitability or synaptic plasticity in SG neurons and revealed that second messengers, such as cAMP and cGMP, play an important role. Recently, cAMP and cGMP were shown to downregulate each other in heart muscle cells. However, involvement of the crosstalk between cAMP and cGMP in neurons is yet to be addressed. Therefore, we investigated whether interaction between cAMP and cGMP modulates synaptic plasticity in SG neurons using slice patch clamp recording from rats. Synaptic activity was measured by excitatory post-synaptic currents (EPSCs) elicited by stimulation onto dorsal root entry zone. Application of 1 mM of 8-bromoadenosine 3,5-cyclic monophosphate (8-Br-cAMP) or 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) for 15 minutes increased EPSCs, which were maintained for 30 minutes. However, simultaneous application of 8-Br-cAMP and 8-Br-cGMP failed to increase EPSCs, which suggested antagonistic cross-talk between two second messengers. Application of 3-isobutyl-1-methylxanthine (IBMX) that prevents degradation of cAMP and cGMP by blocking phosphodiesterase (PDE) increased EPSCs. Co-application of cAMP/cGMP along with IBMX induced additional increase in EPSCs. These results suggest that second messengers, cAMP and cGMP, might contribute to development of chronic pain through the mutual regulation of the signal transduction.


Subject(s)
1-Methyl-3-isobutylxanthine , Adenosine , Animals , Chronic Pain , Guanosine , Myocytes, Cardiac , Neurons , Neurotransmitter Agents , Plastics , Rats , Second Messenger Systems , Signal Transduction , Spinal Nerve Roots , Substantia Gelatinosa
20.
Article in Korean | WPRIM | ID: wpr-22020

ABSTRACT

BACKGROUND AND OBJECTIVES: Cilostazol, a selective inhibitor of phosphodiesterase III (PDE III), prevents inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP) and irreversibly inhibits platelet aggregation and vasodilation. Hence, we performed this prospective randomized study to evaluate the clinical effects of additional cilostazol administration in patients receiving dual antiplatelet therapy after drug-eluting stent (DES) insertion. SUBJECTS AND METHODS: Between December 2003 and June 2006, we enrolled a total 603 consecutive patients who underwent successful percutaneous coronary intervention (PCI) with DES insertion at Dong-A University Hospital. Study patients received dual antiplatelet therapy (aspirin and clopidogrel, n=301) for at least six months or dual antiplatelet therapy (six months) combined with cilostazol medication for one month (triple therapy, n=302) after PCI. We investigated the incidence of major adverse cardiac events (MACE) at one month and six months after the initiation of medical therapy. MACE was defined as a composite of death, myocardial infarction (MI), stent thrombosis, and target lesion revascularization (TLR). Platelet function was evaluated in 66 patients (dual therapy group, n=40; triple therapy group, n=26) using a Chrono-Log platelet aggregometer and the VerifyNow P2Y12 assay system. RESULTS: The MACE rate was 0.66% in the triple therapy group (death only, 0.67%) and 1.67% in the dual therapy group (death, 0.67%; MI, 0.67%; stent thrombosis, 0.99%; TLR, 0.99%) at one month after PCI (p=0.087). At six months, there were no differences in the MACE rate between the two groups (triple group vs. dual group=2.65% vs. 3.99%, p=0.864). In laboratory tests, platelet aggregation induced by agonists of ADP (27.92+/-13.04% vs. 40.9+/-15.78%, p=0.0008), collagen (13.73+/-6.95% vs. 27.43+/-14.87%, p=0.03), and epinephrine (10.38+/-7.82% vs. 15.5+/-10.45%, p=0.0000) were lower in the triple therapy group versus the dual therapy group. However, platelet aggregation induced by agonists of arachidonic acid (3.23+/-1.07% vs. 3.78+/-2.12%, p=0.23) and ristocetin (29.19+/-35.55% vs. 44.78+/-32.65%, p=0.07) and aspirin reaction unit (412.96+/-96.25 vs. 427.93+/-76.24, p=0.48) measured by VerifyNow were not different in the triple group versus the dual group. CONCLUSION: Additional administration of cilostazol did not decrease the MACE rate when compared to dual therapy six months after PCI in patients with DES.


Subject(s)
Adenosine Diphosphate , Adenosine Monophosphate , Arachidonic Acid , Aspirin , Blood Platelets , Collagen , Cyclic Nucleotide Phosphodiesterases, Type 3 , Drug-Eluting Stents , Epinephrine , Humans , Incidence , Myocardial Infarction , Percutaneous Coronary Intervention , Platelet Aggregation , Prospective Studies , Ristocetin , Second Messenger Systems , Stents , Tetrazoles , Thrombosis , Ticlopidine , Vasodilation
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