1.An Experimental Study of the Effect of Histamine on the Rabbit Corpus Cavernosum Tissue.
Yong Tae KIM ; Jae Seung PAICK ; Si Whang KIM
Korean Journal of Urology 1994;35(6):586-591
Penile erection is controlled by adrenergic and nonadrenergic-noncholinergic (NANC) neurotransmission. There are many other substances involved in the corpus cavernosum smooth muscle contraction and relaxation. Among them. histamine is supposed to play an important role to the penile erection mechanisms in both human and animals, but the exact effect and mechanisms are not established. To investigate the effects of histamine on the corpus cavernosum tissue and the intracellular signal transduction mechanisms, we have studied on the rabbit corpus cavernosum using organ bath and the following results were obtained. 1. Corpus cavernosum tissue showed contraction in response to histamine in a dose-dependent manner( ED50 = 2.59 x 0.00001mol). 2. Pheniramine maleate ( 0.00001mol), a H1-receptor antagonist, abolished histamine-induced contraction, but cimetidine(0.00001mol), a H2-receptor antagonist, had no effect on histamine- induced contraction. 3. Histamine-induced contraction was abolished by W-7 (0.0001mol), a calmodulin antagonist, but not affected by staurosporine ( 0.0000001mol), a protein kinase C inhibitor. 4. In the precontracted tissue by phenylephrine histamine produced no relaxation, but pheniramine maleate produced significant relaxation in precontracted tissue It is concluded that in rabbit, histamine induced a dose-dependent contraction mediated by H1- receptors and calcium-calmodulin complex as an intracellular second messenger, but there were few H2-receptors in rabbit corpus cavernosum tissue. By the results of this study, it is supposed that histamine or pheniramine maleate could be used as a drug of intracavernosal injection therapy, but human tissue study, in vivo study and/or in vitro study under electrical stimulation must be preceded.
Animals
;
Baths
;
Calmodulin
;
Electric Stimulation
;
Histamine*
;
Humans
;
Male
;
Muscle, Smooth
;
Penile Erection
;
Pheniramine
;
Phenylephrine
;
Protein Kinase C
;
Relaxation
;
Second Messenger Systems
;
Signal Transduction
;
Staurosporine
;
Synaptic Transmission
2.Spikes with short inter-spike intervals in frog retinal ganglion cells are more correlated with their adjacent neurons' activities.
Wen-Zhong LIU ; Ru-Jia YAN ; Wei JING ; Hai-Qing GONG ; Pei-Ji LIANG
Protein & Cell 2011;2(9):764-771
Correlated firings among neurons have been extensively investigated; however, previous studies on retinal ganglion cell (RGC) population activities were mainly based on analyzing the correlated activities between the entire spike trains. In the present study, the correlation properties were explored based on burst-like activities and solitary spikes separately. The results indicate that: (1) burst-like activities were more correlated with other neurons' activities; (2) burst-like spikes correlated with their neighboring neurons represented a smaller receptive field than that of correlated solitary spikes. These results suggest that correlated burst-like spikes should be more efficient in signal transmission, and could encode more detailed spatial information.
Action Potentials
;
Animals
;
Computer Simulation
;
Darkness
;
Electrophysiology
;
In Vitro Techniques
;
Light
;
Patch-Clamp Techniques
;
Postsynaptic Potential Summation
;
Rana catesbeiana
;
physiology
;
surgery
;
Retina
;
physiology
;
Retinal Ganglion Cells
;
physiology
;
Retinal Neurons
;
physiology
;
Signal Transduction
3.Calcium Sensitization Mechanisms in Gastrointestinal Smooth Muscles.
Journal of Neurogastroenterology and Motility 2016;22(2):213-225
An increase in intracellular Ca2+ is the primary trigger of contraction of gastrointestinal (GI) smooth muscles. However, increasing the Ca2+ sensitivity of the myofilaments by elevating myosin light chain phosphorylation also plays an essential role. Inhibiting myosin light chain phosphatase activity with protein kinase C-potentiated phosphatase inhibitor protein-17 kDa (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation is considered to be the primary mechanism underlying myofilament Ca2+ sensitization. The relative importance of Ca2+ sensitization mechanisms to the diverse patterns of GI motility is likely related to the varied functional roles of GI smooth muscles. Increases in CPI-17 and MYPT1 phosphorylation in response to agonist stimulation regulate myosin light chain phosphatase activity in phasic, tonic, and sphincteric GI smooth muscles. Recent evidence suggests that MYPT1 phosphorylation may also contribute to force generation by reorganization of the actin cytoskeleton. The mechanisms responsible for maintaining constitutive CPI-17 and MYPT1 phosphorylation in GI smooth muscles are still largely unknown. The characteristics of the cell-types comprising the neuroeffector junction lead to fundamental differences between the effects of exogenous agonists and endogenous neurotransmitters on Ca2+ sensitization mechanisms. The contribution of various cell-types within the tunica muscularis to the motor responses of GI organs to neurotransmission must be considered when determining the mechanisms by which Ca2+ sensitization pathways are activated. The signaling pathways regulating Ca2+ sensitization may provide novel therapeutic strategies for controlling GI motility. This article will provide an overview of the current understanding of the biochemical basis for the regulation of Ca2+ sensitization, while also discussing the functional importance to different smooth muscles of the GI tract.
Actin Cytoskeleton
;
Calcium*
;
Gastrointestinal Motility
;
Gastrointestinal Tract
;
Muscle, Smooth*
;
Myofibrils
;
Myosin Light Chains
;
Myosin-Light-Chain Phosphatase
;
Neuroeffector Junction
;
Neurotransmitter Agents
;
Phosphorylation
;
Protein Kinases
;
Signal Transduction
;
Synaptic Transmission
4.Toll-like receptor signal transduction.
Jayalakshmi KRISHNAN ; Kumar SELVARAJOO ; Masa TSUCHIYA ; Gwang LEE ; Sangdun CHOI
Experimental & Molecular Medicine 2007;39(4):421-438
Toll-like receptors (TLRs) are the archetypal pattern recognition receptors in sensing exogenous pathogens. Activation of TLRs is a first line of defense of the immune system, leading to the activation and recruitment of neutrophils and macrophages to sites of infection and enhances antimicrobial activity. The TLR signaling through different intracellular molecules, such as MAP kinases and IkappaB kinases which are conserved signaling elements for many receptors, leads to a distinct set of proinflammatory gene expressions. However, how these pathways differentially and precisely control the transcription of identical genes remains largely unknown. Our review focuses on the details of up-to- date signaling molecules including negative regulators and their role in controlling innate immune response. We also stress the importance of developing systemic approaches for the global understanding of TLR signaling so that appropriate drug therapeutic targets can be identified for regulating inflammatory diseases.
Adaptor Proteins, Signal Transducing/*immunology
;
Animals
;
Humans
;
MAP Kinase Signaling System/*immunology
;
Receptor Cross-Talk
;
Receptors, Interleukin-1/immunology
;
*Signal Transduction
;
Toll-Like Receptors/*immunology
5.Study about target-network of anti-cerebral infarction neuropathy based on theory of neurovascular unit and network pharmacology.
Qingshan LIU ; Liang FANG ; Weiqun WANG ; Ziqian ZHANG ; Hongjun YANG
China Journal of Chinese Materia Medica 2012;37(2):138-141
OBJECTIVEPotention drug-targets on anti-neuropathy of stroke were summarized, and it will provide materials for developing innovation components traditional Chinese medicine on anti-cerebral infarction neuropathy.
METHODThis article had done a series of researching work about neurovascular unit which includes three kinds of cells: neuron, gliacyte,brain microvascular endothelial cell, then signal mechanism of cell death or apoptosis of each section of stroke neuropathy was analysised by the historical documents.
RESULTThere are five important pathways: inflammatory factor-MMPs pathway- Caspases, Ca2+ -mitochondrial pathway-Caspases, Ca2+ -Phospholipase-PI-3K/AK pathway, Ca2+ -radical-MAPK pathway, Ca2+ -NO-protease pathway, among all the nodes, Caspases, Ca2+, NO were the most important ones.
CONCLUSIONDeveloping the multi-mechanism and multilevel of traditional chinese medicine under the guidance of the theories of network pharmacology and neurovascular unit will play an important role in studying the key links of signal-network of stroke neuropathy.
Calcium ; metabolism ; Caspases ; metabolism ; Cerebral Infarction ; metabolism ; prevention & control ; Drug Delivery Systems ; methods ; Humans ; MAP Kinase Signaling System ; Matrix Metalloproteinases ; metabolism ; Medicine, Chinese Traditional ; methods ; Models, Biological ; Pharmacology ; methods ; Phosphatidylinositol 3-Kinases ; metabolism ; Polyneuropathies ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction
6.The Regulation of ERK, GSK3beta and AKT after Acute Ethanol Exposure and Withdrawal in SH-SY5Y Human Neuroblastoma Cell-line.
Jaewoo ROH ; Feng Ji CUI ; Ung Gu KANG
Journal of Korean Neuropsychiatric Association 2010;49(2):241-247
OBJECTIVES: This study aimed to demonstrate the activities and phosphorylation changes induced by acute ethanol treatment and withdrawal conditions in the intracellular signal transduction molecules [such as extracellular signal-regulated kinase (ERK), glycogen synthase kinase 3beta (GSK3beta), and Akt] of the SH-SY5Y neuroblastoma cell line. METHODS: The acute treatment exposed SH-SY5Y cells to 100 mM ethanol, and we took samples 30 minutes, 60 minutes, and 24 hours after initiating this treatment. After 24 hours' continuous ethanol treatment, we initiated ethanol withdrawal, taking samples at 30 minutes and 60 minutes. We assayed the kinase phosphorylations via an immunoblot analysis using phosphorspecific antibodies, quantified by optical densitometry. RESULTS: Ethanol treatment induced a transient increase in phosphorylation of GSK3beta and Akt at 30 minutes but failed to change the phosphorylation level of ERK. Ethanol withdrawal induced a transient ERK phosphorylation increase at 30 minutes, but it had no effect on the phosphorylation of GSK3beta or Akt. CONCLUSION: The results indicate that the ethanol-induced cellular response includes the ERK, GSK3beta, and Akt systems. In particular, the ERK pathway may play a role in the acute withdrawal response. This also suggests that a relatively short exposure to ethanol, such as the 24-hour exposure in this study, can induce functional adaptation within a cell.
Antibodies
;
Cell Line
;
Densitometry
;
Ethanol
;
Glycogen Synthase Kinase 3
;
Glycogen Synthase Kinases
;
Humans
;
MAP Kinase Signaling System
;
Neuroblastoma
;
Phosphorylation
;
Phosphotransferases
;
Signal Transduction
7.The molecular mechanism of fibroblast growth factor 21-inhibited leptin expression in adipocytes.
Di CHEN ; Yan-Yan ZHAO ; Xiang-Yan LIANG ; Li-Jun ZHANG ; Lan-Lan WEI ; Rong XIE ; Xiao-Chun ZHANG ; Xing-Li SU ; Yu-Feng ZHAO
Acta Physiologica Sinica 2020;72(2):175-180
The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.
3T3 Cells
;
Adenylate Kinase
;
Adipocytes
;
metabolism
;
Animals
;
Down-Regulation
;
Fibroblast Growth Factors
;
metabolism
;
Leptin
;
metabolism
;
MAP Kinase Signaling System
;
Mice
;
Phosphorylation
;
Signal Transduction
8.Study of signal transduction pathway in the expression of inflammatory factors stimulated by lipopolysaccharides from Porphyromonas endodontalis in osteoblasts.
Di YANG ; Li-hong QIU ; Ren LI ; Zi-mu LI ; Chen LI
West China Journal of Stomatology 2010;28(2):135-138
OBJECTIVETo quantify the interleukin (IL)-1beta mRNA and IL-6 mRNA expression induced by lipopolysaccharides ([PS) extracted from Porphyromonoas endodontalis (P. endodontalis) in osteoblasts, and to relate P. endodontalis LPS to the bone resorptive pathogenesis in the lesions of chronic apical periodontitis.
METHODSMG63 cells was pretreated with PD98059 or SB203580 for 1 h and then treated with P. endodontolis LPS for 6 h. The expression of IL-1beta mRNA and IL-6 mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) technique.
RESULTSThe production of IL-1beta mRNA induced by P. endodontalis LPS decreased in osteoblasts pretreated with PD98059. Both of the production of IL-1beta mRNA and JL-6 mRNA induced by P. endodontalis LPS decreased in osteoblasts pretreated with SB203580.
CONCLUSIONThe synthesis of IL-1beta mRNA stimulated by Pendodontalis LPS in MG63 probably occur via extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen activated protein kinase (MAPK) signal transduction system. The synthesis of IL-6 mRNA stimulated by P.endodontalis LPS in MG63 probahly occur via p38MAPK signal transduction system.
Humans ; Imidazoles ; Interleukin-6 ; Lipopolysaccharides ; MAP Kinase Signaling System ; Osteoblasts ; Porphyromonas endodontalis ; Pyridines ; RNA, Messenger ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases
9.Different effects of several signal pathway after liver transplantation.
Guo-xun LI ; Nian-qiao GONG ; Qi-fa YE ; Hui GUO
Chinese Journal of Hepatology 2003;11(12):742-744
OBJECTIVESTo explorer the change of several signal pathway and their signal after liver transplantation.
METHODSClassified 34 punctured donor liver samples and 10 normal liver samples as A (no rejection) groups, B (mild/moderate acute rejection) groups, C (serious acute rejection) groups, D (chronic rejection/fibrosis) groups and E (control) groups, MAPK, Ras and p53 were performed immunohistochemistry analysis and image analysis. MAPK and Ras were performed in situ hybridizition. Then image analysis was performed.
RESULTSThe protein expression of MAPK, Ras, increase by turns of A, B and C groups (1.42+/-0.28, 3.88+/-0.87, 6.68+/-0.57 in MAPK; 1.27+/-0.12, 2.80+/-0.30, 3.93+/-0.20 in Ras; corresponding), and decrease by turns of D and E groups (1.49+/-0.37, 0.88+/-0.20 in MAPK; 1.47+/-0.21, 1.01+/-0.12 in Ras; corresponding, F=178.39 in MAPK and 320.59 in Ras, groups B, C vs groups A, D, E, P<0.001 in MAPK and Ras), The protein expression of p53 is higher in treated groups (The results of groups A to E are 2.09+/-0.13, 2.39+/-0.11, 2.03+/-0.19, 2.26+/-0.18 and 0.35+/-0.08, corresponding, F=360.08, groups E vs groups A, B, C, D, P<0.001). Expression of MAPK, Ras mRNA is as same as that of protein.
CONCLUSIONThe MAPKs pathway has role in rejection response after liver transplantation. And it seemed that the MAPKs and p53 are one regulation mechanism for protecting the hepatocyte from damage after liver transplantation.
Humans ; Immunohistochemistry ; In Situ Hybridization ; Liver Transplantation ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases ; analysis ; Signal Transduction ; physiology ; Tumor Suppressor Protein p53 ; analysis ; ras Proteins ; analysis
10.Epidermal growth factor-like domain 7 promotes endothelial cell migration and angiogenesis by activating ERK signaling pathway.
Chinese Journal of Pathology 2015;44(4):270-273
OBJECTIVETo explore the effect of epidermal growth factor-like domain 7(EGFL7) on the migration and angiogenesis of endothelial cells.
METHODSEGFL7 overexpression vectors were constructed and transfected into human microvascular endothelial cells. The expression levels of EGFL7-mRNA and EGFL7 protein were examined by real-time RT-PCR and Western blot. Cell migration was analyzed by the wound healing. The capability of cell to form capillary-like tubes in vitro was evaluated on matrigel assay. Protein expression of p-AKT, AKT, p-ERK and ERK in endothelial cells was detected by Western blot upon transfection with EGFL7 overexpression vectors and vehicle control for 0, 10, 30 and 60 min.
RESULTSMigration and angiogenesis of endothelial cells were notably enhanced by EGFL7 overexpression. ERK pathway was strongly activated by EGFL7, whereas AKT remained constant in endothelial cells. Inhibition of ERK impaired EGFL7 induced ERK activation and endothelial cell migration and angiogenesis.
CONCLUSIONEGFL7 effectively promotes migration and angiogenesis through ERK signaling pathway in endothelial cells.
Blotting, Western ; Cell Movement ; Endothelial Cells ; physiology ; Endothelial Growth Factors ; genetics ; physiology ; Humans ; MAP Kinase Signaling System ; physiology ; Neovascularization, Physiologic ; RNA, Messenger ; metabolism ; Signal Transduction