细胞通路--脑

keyword list 内容 Adult male rats in the cerebral cortex Akt,p-akt Nicotinamide attenuates the ischemic brain injury-induced decrease of Akt activation and Bad phosphorylation. . Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2h after the onset of middle cerebral artery occlusion (MCAO). Brains were collected 24h after MCAO and infarct volumes were analyzed. Nicotinamide significantly reduced the infarct volume in the cerebral cortex. Potential activation was measured by phosphorylation of PDK1 at Ser(241), Akt at Ser(473), and Bad at Ser(136) using Western blot analysis. Nicotinamide prevented the injury-induced decrease of pPDK1, pAkt, and pBad levels. Neurosci Lett. 2011 Jul 8;498(2):105-9. Epub 2011 May 8. uthors Koh PO. rat pheochromocytoma cells caspase-3 p-ERK Paeonol prevents excitotoxicity in rat pheochromocytoma PC12 cells via downregulation of ERK activation and inhibition of apoptosis. Our findings showed that paeonol dose-dependently prevented glutamate-induced cell death as evidenced by cell viability, lactate dehydrogenase release, and trypan blue exclusion. In addition, flow cytometry of propidium iodide-stained cells revealed that paeonol pretreatment reduced the level of glutamate-induced apoptosis in pheochromocytoma cells. Paeonol was also able to decrease the glutamate-induced injury of mitochondria by normalization of mitochondrial membrane potential and cytochrome c release. The glutamate-induced activity of caspase-3 and p-ERK were dose-dependently reduced by paeonol pretreatments. Taken together, our data suggest that paeonol develops its neuroprotective effect against glutamate neurotoxicity through inhibition of the apoptotic signaling pathway and upregulation of the p-ERK pathway. Planta Med. 2011 Oct;77(15):1695-701. Epub 2011 Apr 20. uthors Wang X, et al. Show all Wang X, Zhu G, Yang S, Wang X, Cheng H, Wang F, Li X, Li Q. pheochromocytoma cells neural progenitor cells (NPCs) jnk erk p-38 mGluR5 is involved in proliferation of rat neural progenitor cells exposed to hypoxia with activation of mitogen-activated protein kinase signaling pathway. uthors Zhao L, et al. Show all Zhao L, Jiao Q, Chen X, Yang P, Zhao B, Zheng P, Liu Y. ournal J Neurosci Res. 2012 Feb;90(2):447-60. doi: 10.1002/jnr.22751. Epub 2011 Oct 27. Phosphorylated JNK and ERK increased with the proliferation of NPCs after DHPG and CHPG treatment under hypoxia, while p-p38 level decreased. These results demonstrate that the expression of mGluR5 was upregulated during the proliferation of rat NPCs stimulated by hypoxia in vitro. The activation of the ERK and JNK signaling pathway and the expression of cyclin D1 were increased in this process. These finding suggest the involvement of mGluR5 in rat NPC proliferation and provide a target molecule in neural repair after ischemia/hypoxia Cortex p-ERK p- NF-κB p65 Neurodegeneration, Neuroprotection, and Disease-Oriented Neuroscience H.-L. Zhanga,  HYPERLINK "http://www.sciencedirect.com/science/article/pii/S0306452210016349" \l "cor1#cor1" , 1,  , M. Xua, 1, C. Weia, A.-P. Qina, b, C.-F. Liua, L.-Z. Honga, X.-Y. Zhaoa, J. Liuc, Z.-H. Qina c Texas Tech University Health Science Center–El Paso, Paul Foster School of Medicine, El Paso, TX 79905, USA Accepted 19 December 2010. Available online 24 December 2010. The inhibition of NF-κB signaling pathway by Piog was evaluated by detecting the nuclear translocation of NF-κB p65 with immunohistochemistry and its target gene p53 by real-time PCR, and the expression of phospholated NF-κB p65 (p- NF-κB p65) in primary cultured neurons and the protein levels of IκBα and p-ERK in the ischemic cortex or striatum with Western blotting analysis. rat striatal primary neurons Dopamine promotes striatal neuronal apoptotic death via ERK signaling cascades. Here we investigated in rat striatal primary neurons the mobilization of the mitogen-activated protein kinase (MAPK) signaling pathways after treatment with DA. Instead of observing an elevation of the archetypical pro-cytotoxic MAPKs, p-JNK and p-p38 MAPK, we found that DA, acting through D1 DA receptors, induced a sustained stimulation of the phosphorylated form of extracellular signal-regulated kinase (p-ERK) via a cAMP/protein kinase A (PKA)/Rap1/B-Raf / MAPK/ERK kinase (MEK) pathway. uthors Chen J, et al. Show all Chen J, Rusnak M, Lombroso PJ, Sidhu A. Journal Eur J Neurosci. 2009 Jan;29(2):287-306. Hippocampal P-akt [Effect of recombinant human erythropoietin on hippocampal p-Akt and caspase-9 expressions in rats with status epilepticus and the mechanism]. uthors Wang WP, et al. Show all Wang WP, Shi ZQ, Yu JH, Guo L, Wang L, Han DL, Yuan DC, Zang YZ. Journal Nan Fang Yi Ke Da Xue Xue Bao. 2010 Jan;30(1):64-9. Article in Chinese. Affiliation Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang 050000, China. Adult male SD rats were randomized into control, PTZ, rHuEPO, LY294002 group, and DMSO groups and treated with normal saline (NS), PTZ, PTZ+rHuEPO, PTZ+LY294002+rHuEPO, and PTZ+DMSO+rHuEPO, respectively. The behavioral and electroencephalogram (EEG) changes of the rats were recorded, and the expressions of p-Akt and caspase-9 were detected using immunohistochemistry. The hippocampal expression of caspase-9 mRNA was detected using RT-PCR, and the expressions of Akt and p-Akt proteins were determined with Western blotting. P2 receptor-mediated stimulation of the PI3-K/Akt-pathway in vivo. uthors Franke H, et al. Show all Franke H, Sauer C, Rudolph C, Krügel U, Hengstler JG, Illes P. Journal Glia. 2009 Aug 1;57(10):1031-45. ffiliation Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany. frah@medizin.uni-leipzig.de Therefore, the aim of the present study was to identify the role of the phosphoinositide 3 kinase (PI3-K/Akt) and the mitogen-activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) pathways in P2Y receptor-mediated astrogliosis after traumatic injury and after microinfusion of ADP beta S (P2Y(1,12,13) receptor agonist) into the rat nucleus accumbens (NAc). Mechanical damage and even more the concomitant treatment with ADP beta S, enhanced P2Y(1) receptor-expression in the NAc, which could be reduced by pretreatment with the P2X/Y receptor antagonist PPADS. Quantitative Western blot analysis indicated a significant increase in phosphorylated (p)Akt and pERK1/2 2 h after ADP beta S-microinjection. The involvement of phosphoinositid 3-kinase/Akt pathway in the activation of hypoxia-inducible factor-1alpha in the developing rat brain after hypoxia-ischemia. uthors Li L, et al. Show all Li L, Qu Y, Mao M, Xiong Y, Mu D. Journal Brain Res. 2008 Mar 4;1197:152-8. Epub 2008 Jan 3 To test this hypothesis, we subjected postnatal day 10 rats to HI by ligating common carotid artery followed by hypoxia. Rat brains were collected to detect the expression of HIF-1alpha and its target gene, vascular（血管的） endothelial (内皮)growth factor (VEGF), as well as PI3K/Akt using immunohistochemistry and Western blot analysis. We found that the expression of HIF-1alpha and VEGF was significantly upregulated and peaked at 8 h after HI compared with sham controls. However, the expression of p-Akt peaked at 4 h, earlier than that seen in HIF-1alpha expression. Furthermore, we found that HIF-1alpha and VEGF protein were significantly inhibited after blocking the PI3K/Akt pathway using a specific inhibitor, wortmannin. Our findings suggest that the PI3K/Akt pathway is involved in the regulation of HIF-1alpha and its target gene VEGF in the developing rat brain after HI. hypoxia on neural stem cells (NSCs) erk jnk Hypoxia stimulates proliferation of rat neural stem cells with influence on the expression of cyclin D1 and c-Jun N-terminal protein kinase signaling pathway in vitro. uthors Chen X, et al. Show all Chen X, Tian Y, Yao L, Zhang J, Liu Y. Journal Neuroscience. 2010 Feb 3;165(3):705-14. Epub 2009 Nov 10. The expression of cyclin D1, phosphorylated extracellular signal regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK) and p38 were analyzed by immunoblotting assay. The results showed that hypoxia increased NSCs proliferation in cell amount, diameter of neurospheres, BrdU incorporation and cell division, and the highest proliferation of the NSCs was observed with 12 h hypoxic treatment; hypoxia did not decrease cell death of NSCs; after hypoxic treatment, the expression of cyclin D1 increased, meanwhile P-JNK2 level increased, P-p38 decreased, and no significant change in P-ERK2 level compared to normoxic cultures. JNK inhibitor SP600125 attenuated the increase of cyclin D1 induced by hypoxia. rat striatal primary neurons Dopamine promotes striatal neuronal apoptotic death via ERK signaling cascades. Here we investigated in rat striatal primary neurons the mobilization of the mitogen-activated protein kinase (MAPK) signaling pathways after treatment with DA. Instead of observing an elevation of the archetypical pro-cytotoxic MAPKs, p-JNK and p-p38 MAPK, we found that DA, acting through D1 DA receptors, induced a sustained stimulation of the phosphorylated form of extracellular signal-regulated kinase (p-ERK) via a cAMP/protein kinase A (PKA)/Rap1/B-Raf / MAPK/ERK kinase (MEK) pathway. rat pituitary cell line, GH3 cells Membrane-impermeable estrogen is involved in regulation of calbindin-D9k expression via non-genomic pathways in a rat pituitary cell line, GH3 cells. Taken together, these results demonstrate the involvement of various signaling pathways in E2-induced regulation of CaBP-9k. In addition, ER and G-protein-coupled signaling pathways may play central roles in the non-genomic activities of E2 and that downstream signaling via ERK and Akt are required to evoke ER-mediated induction of CaBP-9k in vitro. uthors Dang VH, et al. Show all Dang VH, Choi KC, Jeung EB. Journal Toxicol In Vitro. 2010 Jun;24(4):1229-36. Epub 2010 Feb 8. αT3-1 cells, an immortalized mouse pituitary cell line of the gonadotrope lineage Divergent Signaling Pathways Requiring Discrete Calcium Signals Mediate Concurrent Activation of Two Mitogen-activated Protein Kinases by Gonadotropin-releasing Hormone* We have demonstrated recently that gonadotropin-releasing hormone (GnRH) receptor occupancy results in activation of extracellular signal-regulated kinase (ERK) through a mechanism requiring calcium influx through L-type calcium channels in αT3-1 cells and primary rat gonadotropes. Further studies were undertaken to explore the signaling mechanisms by which the GnRH receptor is coupled to activation of another member of the MAPK family, c-Jun N-terminal kinase (JNK). Jennifer M. Mulvaney and Mark S. Roberson cortex of the rat brain erk jnk p-38 Temporal and spatial profile of phosphorylated mitogen-activated protein kinase pathways after lateral fluid percussion injury in the cortex of the rat brain. uthors Otani N, et al. Show all Otani N, Nawashiro H, Fukui S, Nomura N, Shima K. Journal J Neurotrauma. 2002 Dec;19(12):1587-96 The purpose of this study was to investigate the temporal expression and topographic distribution of the activated MAPK pathways including extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK following traumatic brain injury (TBI) in the cortex of the rat brain. Adult male Sprague-Dawley rats (300-400 g) were subjected to lateral fluid percussion injury of moderate severity (3.5-4.0 atm) using the Dragonfly device model (no. HPD-1700). Phosphorylated-MAPK protein levels were quantified using Western blot analysis. Topographic distribution of immunoreactivity for phosphorylated-MAPK was examined using immunohistochemistry. BV-2 microglial cells microglia, neuroinflammation, nitrite, inducible nitric oxide synthase, Kamebakaurin Anti-neuroinflammatory Activity of Kamebakaurin From Isodon japonicus via Inhibition of c-Jun NH2-Terminal Kinase and p38 Mitogen-Activated Protein Kinase Pathway in Activated Microglial Cells The present study investigated the effects of Kamebakaurin (KMBK), a kaurane diterpene isolated from Isodon japonicus HARA (Labiatae), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated cytotoxicity in rat primary microglial cultures and the BV-2 cell line. KMBK significantly inhibited the LPSinduced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells. The mRNA and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxycenase- 2 (COX-2) were also decreased dose-dependently. Furthermore KMBK inhibited the JNK and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated BV-2 microglial cells. Considering the results obtained, the present study authenticated the potential benefits of KMBK as a therapeutic target in ameliorating microglia-mediated neuroinflammatory diseases. CHO rat nucleus accumbens AKT ERK1/2 GSK-3 Signaling Pathways Leading to Phosphorylation of Akt and GSK-3_ by Activation of Cloned Human and Rat Cerebral D2 and D3 Receptors CHO cells expressing human (h) D2L or D3 receptors (4.6 and 12 pmol/mg protein, respectively) were grown in Ham’s F12 medium or Dulbecco’s modified Eagle’s medium as described previously (Cussac et al., 1999). For determination of ERK1/2, Akt, and GSK-3_ phosphorylation, In Vivo Experiments. Male Wistar Han rats (226–250 g; Charles River Laboratories Inc., L’arbresle, France) received a single injection of quinelorane (0.16 mg/kg s.c.) 10 min before rapid removal of brains, which were immerged for 15 s in liquid nitrogen then laid over a dry ice slab. Brains were stored at _80°C until use. Mounted on a Peltier refrigerated sliding plate, sections were cut and the nucleus accumbens isolated using a cooled 1.8-mm diameter punch. Frozen samples were sonicated in a warmed Laemmli sample buffer containing SDS (1%) to reach a concentration of _2 _g/_l of protein. Samples were then boiled for 3 min at 95°C and stored at _80°C. For antagonist experiments, raclopride (0.16 mg/kg s.c.) or vehicle (1 ml/kg s.c.) was administrated 30 min before quinelorane. rat pituitary cell line GH3 ERK 1/2 Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway European Journal of Endocrinology (2004) 151 233–240 Objectives: Ghrelin is a brain-gut peptide with GH-releasing and appetite-inducing activities and a widespread tissue distribution. Ghrelin is the endogenous ligand of the GH secretagogue receptor type 1a (GHS-R1a), and both ghrelin and the GHS-R1a are expressed in the pituitary. There are conflicting data regarding the effects of ghrelin on cell proliferation. A positive effect on proliferation and activation of the mitogen-activated protein kinase (MAPK) pathway has been found in hepatoma, adipose, cardiomyocyte and prostate cell lines. However, ghrelin has also been shown to have antiproliferative effects on breast, lung and thyroid cell lines. We therefore examined the effect of ghrelin on the rat pituitary cell line GH3. Methods: RT-PCR was used for the detection of GHS-R1a and pre-proghrelin mRNA expression in GH3 cells. The effect of ghrelin on cell proliferation was studied using [3H]thymidine incorporation; cell counting and the activation of the MAPK pathway were studied using immunoblotting and inhibitors of the extracellular signal-regulated kinase 1 and 2 (ERK 1/2), protein kinase C (PKC) and tyrosine phosphatase pathways Pituitaries LH ERK JNK Regulation of Intracellular Signaling Cascades by GNRH Pulse Frequency in the Rat Pituitary: Roles for CaMK II, ERK, and JNK Activation1 Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with faster frequencies favoring Lhb transcription and slower favoring Fshb. Various intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2), ERK, and JNK. We examined whether activation of these pathways is regulated by GNRH pulse frequency in vivo. BIOLOGY OF REPRODUCTION 79, 947–953 (2008) Laura L. Burger,2 Daniel J. Haisenleder, Kevin W. Aylor, and John C. Marshall neocortex, prefrontal cortex striatum, hippocampus amygdala. ERK P-38 JNK Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions Chang-peng Shen1, Yelena Tsimberg1, Christopher Salvadore2 and Emanuel Meller*1 BMC Neuroscience The mitogen-activated protein kinases (MAPKs) have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2) has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P) state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6), were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE) binding (CREB) protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results: A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3) were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/ 2 and P-MKK4 (activators of the Erk and JNK pathways, respectively) were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold). Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex) areas Akt; FoxO4; GSK-3; ischemic tolerance; MDM2; PC12 cells Involvement of Akt in preconditioning-induced tolerance to ischemia in PC12 cells Journal of Cerebral Blood Flow & Metabolism (2006) 26, 1323–1331 Joe¨lle A Hillion1, YiXin Li1, Dragan Maric2, Asako Takanohashi1, Dace Klimanis1, Jeffrey L Barker2 and John M Hallenbeck1 The serine–threonine protein kinase Akt has been identified as an important mediator of cell survival able to counteract apoptotic stimuli. However, hibernation, a model of natural tolerance to cerebral ischemia, is associated with downregulation of Akt. We previously established a model of ischemic tolerance in a PC12 cell line and using this model we now addressed the question whether ischemic tolerance also downregulates Akt in PC12 cells. Kinetic studies showed decreased Akt phosphorylation in tolerized cells. Similarly, phosphorylated levels of three major targets of Akt and well-known proapoptotic factors, the glycogen synthase kinase 3 (GSK-3), a Forkhead family member, FoxO4, and the protein murine double minute 2 (MDM2), all inactivated upon phosphorylation by Akt, were decreased in preconditioned cells Electroacupuncture; Akt; phospho-Akt; brain; rat Enhanced expression of phospho-Akt by electro-acupuncture in normal rat brain investigate a detailed molecular mechanism of EA stimulation, an induction of phospho-Akt (p-Akt) was examined in normal ad