LIVIVO - Search results -

Search results

Result 1 - 10 of total 21

Search options

Article ; Online: Accumulation of high molecular weight kininogen in the brains of Alzheimer's disease patients may affect microglial function by altering phagocytosis and lysosomal cathepsin activity.

Zamolodchikov, Daria / Duffield, Michael / Macdonald, Lynn E / Alessandri-Haber, Nicole

Alzheimer's & dementia : the journal of the Alzheimer's Association

2022 Volume 18, Issue 10, Page(s) 1919–1929

Abstract: Increased activation of the contact system protein high molecular weight kininogen (HK) has been shown in plasma and cerebrospinal fluid of Alzheimer's disease (AD) patients, but its potential role in the brain has not been explored. We assessed HK ... ...

Abstract	Increased activation of the contact system protein high molecular weight kininogen (HK) has been shown in plasma and cerebrospinal fluid of Alzheimer's disease (AD) patients, but its potential role in the brain has not been explored. We assessed HK levels in brain tissue from 20 AD patients and controls and modeled the effects of HK on microglia-like cells in culture. We show increased levels of HK in the hippocampus of AD patients, which colocalized with amyloid beta (Aβ) deposits and activated microglia. Treatment of microglia with HK led to cell clustering and elevated levels of phagocytosed Aβ. We demonstrate that microglia internalize HK and traffic it to lysosomes, which is accompanied by reduced activity of lysosomal cathepsins L and S. Our results suggest that HK accumulation in the AD hippocampus may alter microglial uptake and degradation of Aβ fibrils, possibly contributing to microglial dysfunction in AD.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Brain/metabolism ; Cathepsins/metabolism ; Cathepsins/pharmacology ; Kininogen, High-Molecular-Weight/metabolism ; Kininogen, High-Molecular-Weight/pharmacology ; Lysosomes/metabolism ; Microglia/metabolism ; Phagocytosis
Chemical Substances	Amyloid beta-Peptides ; Cathepsins (EC 3.4.-) ; Kininogen, High-Molecular-Weight
Language	English
Publishing date	2022-01-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12531
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6316: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 540: Show issues

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: AdRoit is an accurate and robust method to infer complex transcriptome composition.

Yang, Tao / Alessandri-Haber, Nicole / Fury, Wen / Schaner, Michael / Breese, Robert / LaCroix-Fralish, Michael / Kim, Jinrang / Adler, Christina / Macdonald, Lynn E / Atwal, Gurinder S / Bai, Yu

Communications biology

2021 Volume 4, Issue 1, Page(s) 1218

Abstract: Bulk RNA sequencing provides the opportunity to understand biology at the whole transcriptome level without the prohibitive cost of single cell profiling. Advances in spatial transcriptomics enable to dissect tissue organization and function by genome- ... ...

Abstract	Bulk RNA sequencing provides the opportunity to understand biology at the whole transcriptome level without the prohibitive cost of single cell profiling. Advances in spatial transcriptomics enable to dissect tissue organization and function by genome-wide gene expressions. However, the readout of both technologies is the overall gene expression across potentially many cell types without directly providing the information of cell type constitution. Although several in-silico approaches have been proposed to deconvolute RNA-Seq data composed of multiple cell types, many suffer a deterioration of performance in complex tissues. Here we present AdRoit, an accurate and robust method to infer the cell composition from transcriptome data of mixed cell types. AdRoit uses gene expression profiles obtained from single cell RNA sequencing as a reference. It employs an adaptive learning approach to alleviate the sequencing technique difference between the single cell and the bulk (or spatial) transcriptome data, enhancing cross-platform readout comparability. Our systematic benchmarking and applications, which include deconvoluting complex mixtures that encompass 30 cell types, demonstrate its preferable sensitivity and specificity compared to many existing methods as well as its utilities. In addition, AdRoit is computationally efficient and runs orders of magnitude faster than most methods.
MeSH term(s)	Gene Expression Profiling/methods ; Genome ; Sensitivity and Specificity ; Transcriptome
Language	English
Publishing date	2021-10-22
Publishing country	England
Document type	Journal Article
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-02739-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: A Short Isoform of Coagulation Factor XII mRNA Is Expressed by Neurons in the Human Brain.

Zamolodchikov, Daria / Bai, Yu / Tang, Yajun / McWhirter, John R / Macdonald, Lynn E / Alessandri-Haber, Nicole

Neuroscience

2019 Volume 413, Page(s) 294–307

Abstract: Coagulation factor XII (FXII) is synthesized in the liver and secreted into the circulation, where it initiates the contact activation system. Although typically thought to be restricted to the circulation, FXII protein has been found in the brain of ... ...

Abstract	Coagulation factor XII (FXII) is synthesized in the liver and secreted into the circulation, where it initiates the contact activation system. Although typically thought to be restricted to the circulation, FXII protein has been found in the brain of Alzheimer's disease (AD) and multiple sclerosis patients. Moreover, activation of the contact system has been detected in the cerebrospinal fluid of these patients as well as in the brain of healthy and AD individuals. While FXII protein has been detected in the brain, its source and its potential role in brain physiology and/or pathology have not been elucidated. Using in situ hybridization, we show that a shorter FXII mRNA isoform is expressed by neurons in human brain and in the brain of FXII humanized mice, with the highest expression observed in pyramidal neurons. This shorter FXII transcript contains an open reading frame coding for the portion of FXII that spans its proline-rich and catalytic domains (FXII
MeSH term(s)	Animals ; Animals, Genetically Modified ; Brain/metabolism ; Cells, Cultured ; Factor XII/genetics ; Factor XII/metabolism ; Hepatocyte Growth Factor/metabolism ; Kallikreins/blood ; Liver/metabolism ; Mice, 129 Strain ; Mice, Inbred C57BL ; Neurons/metabolism ; RNA Isoforms/metabolism ; RNA, Messenger/metabolism
Chemical Substances	RNA Isoforms ; RNA, Messenger ; Hepatocyte Growth Factor (67256-21-7) ; Factor XII (9001-30-3) ; Kallikreins (EC 3.4.21.-)
Language	English
Publishing date	2019-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2019.05.040
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1215: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: AdRoit is an accurate and robust method to infer complex transcriptome composition

Tao Yang / Nicole Alessandri-Haber / Wen Fury / Michael Schaner / Robert Breese / Michael LaCroix-Fralish / Jinrang Kim / Christina Adler / Lynn E. Macdonald / Gurinder S. Atwal / Yu Bai

Communications Biology, Vol 4, Iss 1, Pp 1-

2021 Volume 14

Abstract: Yang et al. present AdRoit, a method for deconvoluting bulk RNA sequencing and spatial transcriptomics data. AdRoit performs well on datasets from complex tissues with many different cell types. ...

Abstract	Yang et al. present AdRoit, a method for deconvoluting bulk RNA sequencing and spatial transcriptomics data. AdRoit performs well on datasets from complex tissues with many different cell types.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: TRP channels: targets for the relief of pain.

Levine, Jon D / Alessandri-Haber, Nicole

Biochimica et biophysica acta

2007 Volume 1772, Issue 8, Page(s) 989–1003

Abstract: Patients with inflammatory or neuropathic pain experience hypersensitivity to mechanical, thermal and/or chemical stimuli. Given the diverse etiologies and molecular mechanisms of these pain syndromes, an approach to developing successful therapies may ... ...

Abstract	Patients with inflammatory or neuropathic pain experience hypersensitivity to mechanical, thermal and/or chemical stimuli. Given the diverse etiologies and molecular mechanisms of these pain syndromes, an approach to developing successful therapies may be to target ion channels that contribute to the detection of thermal, mechanical and chemical stimuli and promote the sensitization and activation of nociceptors. Transient Receptor Potential (TRP) channels have emerged as a family of evolutionarily conserved ligand-gated ion channels that contribute to the detection of physical stimuli. Six TRPs (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8 and TRPA1) have been shown to be expressed in primary afferent nociceptors, pain sensing neurons, where they act as transducers for thermal, chemical and mechanical stimuli. This short review focuses on their contribution to pain hypersensitivity associated with peripheral inflammatory and neuropathic pain states.
MeSH term(s)	Analgesics/chemical synthesis ; Analgesics/metabolism ; Analgesics/therapeutic use ; Animals ; Calcium Channels/metabolism ; Calcium Channels/physiology ; Drug Design ; Humans ; Models, Biological ; Nerve Tissue Proteins/agonists ; Nerve Tissue Proteins/metabolism ; Nerve Tissue Proteins/physiology ; Neurons, Afferent/metabolism ; Neurons, Afferent/physiology ; Pain/drug therapy ; TRPA1 Cation Channel ; TRPM Cation Channels/agonists ; TRPM Cation Channels/metabolism ; TRPM Cation Channels/physiology ; TRPV Cation Channels/agonists ; TRPV Cation Channels/metabolism ; TRPV Cation Channels/physiology ; Transient Receptor Potential Channels/agonists ; Transient Receptor Potential Channels/metabolism ; Transient Receptor Potential Channels/physiology
Chemical Substances	Analgesics ; Calcium Channels ; Nerve Tissue Proteins ; TRPA1 Cation Channel ; TRPA1 protein, human ; TRPM Cation Channels ; TRPM8 protein, human ; TRPV Cation Channels ; Transient Receptor Potential Channels
Language	English
Publishing date	2007-08
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2007.01.008
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.247: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4-/- mice.

Chen, Xiaojie / Alessandri-Haber, Nicole / Levine, Jon D

Molecular pain

2007 Volume 3, Page(s) 31

Abstract: Inflammatory mediators can directly sensitize primary afferent nociceptors to mechanical and osmotic stimuli. Sensitized nociceptors have a lowered threshold of activation and increased spontaneous activity, which result in symptoms of hyperalgesia and ... ...

Abstract	Inflammatory mediators can directly sensitize primary afferent nociceptors to mechanical and osmotic stimuli. Sensitized nociceptors have a lowered threshold of activation and increased spontaneous activity, which result in symptoms of hyperalgesia and pain, respectively. The transient receptor potential vanilloid 4 (TRPV4) ligand-gated ion channel has been implicated in the hyperalgesia for mechanical and osmotic stimuli associated with inflammatory states. To investigate whether TRPV4 directly contributes to the mechanisms of inflammatory mediator sensitization of C-fiber nociceptors, we compared the effect of the injection of simplified inflammatory soup (prostaglandin E2 and serotonin) into the mechanical receptive fields of C-fibers in TRPV4+/+ and TRPV4-/- mice in vivo. Following the injection of the soup, the percentage of C-fibers responding to a hypotonic stimulus and the magnitude of the response was significantly greater in TRPV4+/+ mice compared to TRPV4-/- mice. Moreover, in response to simplified inflammatory soup only C-fibers from TRPV4+/+ mice exhibited increased spontaneous activity and decreased mechanical threshold. These marked impairments in the response of C-fibers in TRPV4-/- mice demonstrate the importance of TRPV4 in nociceptor sensitization; we suggest that TRPV4, as TRPV1, underlies the nociceptive effects of multiple inflammatory mediators on primary afferent.
MeSH term(s)	Action Potentials/drug effects ; Action Potentials/genetics ; Afferent Pathways/drug effects ; Afferent Pathways/physiopathology ; Animals ; Dinoprostone ; Disease Models, Animal ; Hyperalgesia/chemically induced ; Hyperalgesia/genetics ; Hyperalgesia/physiopathology ; Hypotonic Solutions/pharmacology ; Inflammation/chemically induced ; Inflammation/genetics ; Inflammation/physiopathology ; Inflammation Mediators/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Fibers, Unmyelinated/drug effects ; Nerve Fibers, Unmyelinated/metabolism ; Neural Conduction/drug effects ; Neural Conduction/genetics ; Neurons, Afferent/drug effects ; Neurons, Afferent/metabolism ; Nociceptors/drug effects ; Nociceptors/physiopathology ; Pain/chemically induced ; Pain/genetics ; Pain/physiopathology ; Pain Measurement ; Pain Threshold/drug effects ; Physical Stimulation ; Serotonin ; Spinal Nerve Roots/drug effects ; Spinal Nerve Roots/physiopathology ; Stimulation, Chemical ; TRPV Cation Channels/genetics
Chemical Substances	Hypotonic Solutions ; Inflammation Mediators ; TRPV Cation Channels ; Trpv4 protein, mouse ; Serotonin (333DO1RDJY) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2007-10-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2174252-2
ISSN	1744-8069 ; 1744-8069
ISSN (online)	1744-8069
ISSN	1744-8069
DOI	10.1186/1744-8069-3-31
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Generation of a pain memory in the primary afferent nociceptor triggered by PKCε activation of CPEB.

Bogen, Oliver / Alessandri-Haber, Nicole / Chu, Carissa / Gear, Robert W / Levine, Jon D

The Journal of neuroscience : the official journal of the Society for Neuroscience

2012 Volume 32, Issue 6, Page(s) 2018–2026

Abstract: Isolectin B(4)-positive [IB(4)(+)] primary afferent nociceptors challenged with an inflammatory or neuropathic insult develop a PKCε-dependent long-lasting hyperalgesic response to a subsequent challenge by the proinflammatory cytokine prostaglandin E(2) ...

Abstract	Isolectin B(4)-positive [IB(4)(+)] primary afferent nociceptors challenged with an inflammatory or neuropathic insult develop a PKCε-dependent long-lasting hyperalgesic response to a subsequent challenge by the proinflammatory cytokine prostaglandin E(2) (PGE(2)), a phenomenon known as hyperalgesic priming. Here we demonstrate that the neuroplasticity underlying nociceptor priming requires 72 h to be established; rats that have been challenged with the inflammatory mediator TNFα 24 or 48 h ahead of PGE(2) do not show the enhanced and prolonged hyperalgesic response by which primed IB(4)(+)-nociceptors are being characterized. Moreover, as the underlying plasticity can be interrupted by the peripheral administration of the protein translation inhibitor anisomycin it is reflected by changes in the peripheral protein expression pattern. Finally, the induction of priming by the selective PKCε agonist, psi ε receptor for activated c kinase (ψεRACK) can be prevented, but not reversed by intrathecal injections of antisense oligodeoxynucleotides for the cytoplasmic polyadenylation element binding protein (CPEB) mRNA, a master regulator of protein translation that coimmunoprecipitated with PKCε and is almost exclusively expressed by IB(4)(+)-nociceptors. Our results suggest that CPEB is downstream of PKCε in the cellular signaling cascade responsible for the induction of priming, raising the intriguing possiblity that prion-like misfolding could be a responsible mechanism for the chronification of pain.
MeSH term(s)	Animals ; Hyperalgesia/enzymology ; Hyperalgesia/metabolism ; Hyperalgesia/pathology ; Male ; Memory/physiology ; Models, Neurological ; Neurons, Afferent/enzymology ; Neurons, Afferent/metabolism ; Neurons, Afferent/pathology ; Nociceptors/metabolism ; Nociceptors/physiology ; Pain/enzymology ; Pain/metabolism ; Pain/pathology ; Pain Measurement/methods ; Protein Kinase C-epsilon/metabolism ; Protein Kinase C-epsilon/physiology ; RNA-Binding Proteins/metabolism ; RNA-Binding Proteins/physiology ; Rats ; Rats, Sprague-Dawley
Chemical Substances	CPEB1 protein, rat ; RNA-Binding Proteins ; Protein Kinase C-epsilon (EC 2.7.11.13)
Language	English
Publishing date	2012-02-09
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.5138-11.2012
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1668: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: TRPC1 and TRPC6 channels cooperate with TRPV4 to mediate mechanical hyperalgesia and nociceptor sensitization.

Alessandri-Haber, Nicole / Dina, Olayinka A / Chen, Xiaoje / Levine, Jon D

The Journal of neuroscience : the official journal of the Society for Neuroscience

2009 Volume 29, Issue 19, Page(s) 6217–6228

Abstract: ... of diverse etiologies, presumably as part of a mechanoreceptor signaling complex (Alessandri-Haber et al ...

Abstract	The transient receptor potential vanilloid 4 (TRPV4) contributes to mechanical hyperalgesia of diverse etiologies, presumably as part of a mechanoreceptor signaling complex (Alessandri-Haber et al., 2008). To investigate the hypothesis that a functional interaction between TRPV4 and stretch-activated ion channels (SACs) is involved in this mechanical transduction mechanism, we used a selective SACs inhibitor, GsMTx-4. Intradermal injection of GsMTx-4 in the rat hindpaw reversed the mechanical hyperalgesia induced by intradermal injection of inflammatory mediators. In vivo single fiber recordings showed that GsMTx-4 reversed inflammatory mediator-induced decrease in mechanical threshold in half of sensitized C-fibers. Furthermore, GsMTx-4 reduced hyperalgesia to both mechanical and hypotonic stimuli in different models of inflammatory and neuropathic pain, although it had no effect on baseline mechanical nociceptive thresholds. TRPC1 and TRPC6, two GsMTx-4-sensitive SACs, are expressed in dorsal root ganglion (DRG) neurons. Single-cell reverse transcription-PCR showed that messenger RNAs for TRPV4, TRPC1, and TRPC6 are frequently coexpressed in DRG neurons. Spinal intrathecal administration of oligodeoxynucleotides antisense to TRPC1 and TRPC6, like that to TRPV4, reversed the hyperalgesia to mechanical and hypotonic stimuli induced by inflammatory mediators without affecting baseline mechanical nociceptive threshold. However, antisense to TRPC6, but not to TRPC1, reversed the mechanical hyperalgesia induced by a thermal injury or the TRPV4-selective agonist 4alpha-PDD (4 alpha-phorbol 12,13-didecanoate). We conclude that TRPC1 and TRPC6 channels cooperate with TRPV4 channels to mediate mechanical hyperalgesia and primary afferent nociceptor sensitization, although they may have distinctive roles.
MeSH term(s)	Animals ; Foot ; Ganglia, Spinal/physiology ; Gene Expression ; Hindlimb ; Hyperalgesia/chemically induced ; Hyperalgesia/physiopathology ; Intercellular Signaling Peptides and Proteins ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/physiology ; Oligodeoxyribonucleotides, Antisense/metabolism ; Pain Threshold/physiology ; Peptides/pharmacology ; Phorbol Esters ; Physical Stimulation ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Spider Venoms/pharmacology ; TRPC Cation Channels/metabolism ; TRPC6 Cation Channel ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism
Chemical Substances	Intercellular Signaling Peptides and Proteins ; MTx4 protein, Grammostola spatulata ; Oligodeoxyribonucleotides, Antisense ; Peptides ; Phorbol Esters ; RNA, Messenger ; Spider Venoms ; TRPC Cation Channels ; TRPC6 Cation Channel ; TRPV Cation Channels ; Trpc6 protein, mouse ; Trpc6 protein, rat ; Trpv4 protein, mouse ; transient receptor potential cation channel, subfamily C, member 1 ; phorbol-12,13-didecanoate (24928-17-4)
Language	English
Publishing date	2009-05-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.0893-09.2009
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1668: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: PLC-beta 3 signals upstream of PKC epsilon in acute and chronic inflammatory hyperalgesia.

Joseph, Elizabeth K / Bogen, Oliver / Alessandri-Haber, Nicole / Levine, Jon D

Pain

2007 Volume 132, Issue 1-2, Page(s) 67–73

Abstract: While protein kinase C epsilon has been shown to contribute to acute and chronic mechanical hyperalgesia, its upstream signaling pathway has received little attention. Since phospholipase C can signal to PKC epsilon and has been implicated in nociceptor ... ...

Abstract	While protein kinase C epsilon has been shown to contribute to acute and chronic mechanical hyperalgesia, its upstream signaling pathway has received little attention. Since phospholipase C can signal to PKC epsilon and has been implicated in nociceptor sensitization, we tested if it is upstream of PKC epsilon in mechanisms underlying primary mechanical hyperalgesia. In the rat, the PKC epsilon-dependent mechanical hyperalgesia and hyperalgesic priming (i.e., a form of chronic latent enhanced hyperalgesia) induced by carrageenan were attenuated by a non-selective PLC inhibitor U-73122. A lipid mediator of PLC signaling, l-alpha-lysophosphatidylcholine produced dose-dependent mechanical hyperalgesia and hyperalgesic priming, which was attenuated by EAVSLKPT, a selective PKC epsilon inhibitor. However, U-73122 did not attenuate hyperalgesia induced by psi epsilon RACK, a selective PKC epsilon activator. Antisense to PLC-beta 3 isoform, which was found in small-diameter dorsal root ganglion neurons, also attenuated carrageenan-induced acute and chronic-latent hyperalgesia. These studies support the suggestion that PLC-beta 3 is an important upstream signaling molecule for PKC epsilon-mediated acute and chronic inflammatory pain.
MeSH term(s)	Acute Disease ; Animals ; Chronic Disease ; Hyperalgesia/physiopathology ; Inflammation/physiopathology ; Isoenzymes/metabolism ; Male ; Phospholipase C beta ; Protein Kinase C-epsilon/metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Touch ; Type C Phospholipases/metabolism
Chemical Substances	Isoenzymes ; Protein Kinase C-epsilon (EC 2.7.11.13) ; Type C Phospholipases (EC 3.1.4.-) ; Phospholipase C beta (EC 3.1.4.11)
Language	English
Publishing date	2007-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1016/j.pain.2007.01.027
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1158: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4 -/- mice

Levine Jon D / Alessandri-Haber Nicole / Chen Xiaojie

Molecular Pain, Vol 3, Iss 1, p

2007 Volume 31

Abstract: Abstract Inflammatory mediators can directly sensitize primary afferent nociceptors to mechanical and osmotic stimuli. Sensitized nociceptors have a lowered threshold of activation and increased spontaneous activity, which result in symptoms of ... ...

Abstract	Abstract Inflammatory mediators can directly sensitize primary afferent nociceptors to mechanical and osmotic stimuli. Sensitized nociceptors have a lowered threshold of activation and increased spontaneous activity, which result in symptoms of hyperalgesia and pain, respectively. The transient receptor potential vanilloid 4 (TRPV4) ligand-gated ion channel has been implicated in the hyperalgesia for mechanical and osmotic stimuli associated with inflammatory states. To investigate whether TRPV4 directly contributes to the mechanisms of inflammatory mediator sensitization of C-fiber nociceptors, we compared the effect of the injection of simplified inflammatory soup (prostaglandin E 2 and serotonin) into the mechanical receptive fields of C-fibers in TRPV4 +/+ and TRPV4 -/- mice in vivo . Following the injection of the soup, the percentage of C-fibers responding to a hypotonic stimulus and the magnitude of the response was significantly greater in TRPV4 +/+ mice compared to TRPV4 -/- mice. Moreover, in response to simplified inflammatory soup only C-fibers from TRPV4 +/+ mice exhibited increased spontaneous activity and decreased mechanical threshold. These marked impairments in the response of C-fibers in TRPV4 -/- mice demonstrate the importance of TRPV4 in nociceptor sensitization; we suggest that TRPV4, as TRPV1, underlies the nociceptive effects of multiple inflammatory mediators on primary afferent.
Keywords	Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	333
Language	English
Publishing date	2007-10-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED