INT136304

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Context Info
Confidence 0.59
First Reported 2006
Last Reported 2010
Negated 1
Speculated 1
Reported most in Body
Documents 54
Total Number 57
Disease Relevance 48.42
Pain Relevance 7.40

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

plasma membrane (Aqp4) protein complex (Aqp4) transmembrane transport (Aqp4)
cytoplasm (Aqp4)
Anatomy Link Frequency
astrocytes 6
retina 5
brain 5
eyes 3
central nervous system 2
Aqp4 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Spinal cord 301 99.76 Very High Very High Very High
Central nervous system 298 99.60 Very High Very High Very High
Demyelination 638 99.32 Very High Very High Very High
ischemia 111 98.82 Very High Very High Very High
Neuritis 100 98.00 Very High Very High Very High
Multiple sclerosis 410 97.90 Very High Very High Very High
hyperexcitability 23 95.60 Very High Very High Very High
Sumatriptan 5 91.04 High High
Inflammation 251 90.88 High High
Lamotrigine 5 90.36 High High
Disease Link Frequency Relevance Heat
Injury 573 99.90 Very High Very High Very High
Stress 92 99.88 Very High Very High Very High
Targeted Disruption 88 99.84 Very High Very High Very High
Hypoxia 81 99.66 Very High Very High Very High
Ganglion Cysts 159 99.64 Very High Very High Very High
Hypertrophy 142 99.60 Very High Very High Very High
Hydrocephalus 129 99.56 Very High Very High Very High
Neuromyelitis Optica 1197 99.52 Very High Very High Very High
Demyelinating Disease 1102 99.32 Very High Very High Very High
Ocular Hypertension 1305 99.24 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Contrary to the findings of Huber et al., in our studies we found no significant inhibition of AQP4 water permeability by any of the compounds at concentrations up to 100 microM.
Negative_regulation (inhibition) of AQP4
1) Confidence 0.59 Published 2008 Journal Bioorg. Med. Chem. Section Abstract Doc Link 18572411 Disease Relevance 0.15 Pain Relevance 0.14
An imbalanced reduction of AQP4 levels may therefore impair retinal K+ buffering and uncontrolled increases in [K+]o may induce uncontrolled hyperexcitability and abnormal synchronization of retinal neurons.
Negative_regulation (reduction) of AQP4 in neurons associated with hyperexcitability
2) Confidence 0.57 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2559817 Disease Relevance 0.20 Pain Relevance 0.05
In addition, AQP4 deletion in mice is neuroprotective in a transient ischemia model of retinal injury [37] and hypoxia induced a marked decrease in AQP4 mRNA levels in astrocytes in vitro [38], suggesting that the reduction of AQP4 levels may be a beneficial mechanism.
Negative_regulation (reduction) of AQP4 in astrocytes associated with hypoxia, ischemia and injury
3) Confidence 0.57 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2559817 Disease Relevance 1.31 Pain Relevance 0.13
Five out of 7 rats (71%) showed a significant reduction in mRNA (54±11%, p<0.001 versus HEPES-injected or control, Figure 2A), and there was a similar reduction in AQP4 mRNA upon elevation of IOP in six out nine rats (67%, 62±12, p=0.001, Figure 2B).
Negative_regulation (reduction) of AQP4 mRNA associated with ocular hypertension
4) Confidence 0.57 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2559817 Disease Relevance 0.93 Pain Relevance 0
The lack of selective AQP4 inhibitors also hampers a quicker evaluation of whether AQP4 inhibition will prevent hypertrophy upon elevation of IOP.
Spec (whether) Negative_regulation (inhibition) of AQP4 associated with hypertrophy and ocular hypertension
5) Confidence 0.57 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2559817 Disease Relevance 1.70 Pain Relevance 0.12
NMO is an autoimmune disease characterized by severe optic neuritis and transverse myelitis where serum from patients is enriched with anti-AQP4 antibodies leading to loss of AQP4 in the active perivascular NMO lesions.
Negative_regulation (loss) of AQP4 in optic associated with neuromyelitis optica, transverse myelitis, autoimmune disease, optic neuritis and neuritis
6) Confidence 0.57 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2559817 Disease Relevance 1.75 Pain Relevance 0.17
Therefore it is possible that the elevation of IOP would inhibit ubiquitin transport to axons and thus explain the attenuated ubiquitination in axons, whereas the accumulation of ubiquitin in retina could account for the enhanced ubiquitination and the downregulation of AQP4 protein.
Negative_regulation (downregulation) of AQP4 protein in retina associated with ocular hypertension
7) Confidence 0.57 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2559817 Disease Relevance 0.78 Pain Relevance 0
As shown in Figure 2A, ET-1 injection resulted in a decrease in AQP4 mRNA as determined by Q-PCR.
Negative_regulation (decrease) of AQP4 mRNA
8) Confidence 0.57 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2559817 Disease Relevance 1.01 Pain Relevance 0
As shown in Figure 2A, ONC resulted in a decrease in AQP4 protein (60±10, 63±10, and 38±10, p<0.001 at days 2, 7, and 14, respectively, Figure 2A,B, n=7), and there as a similar reduction in AQP4 mRNA (~40%), as determined by Q-PCR (61±5%, 60±8%, and 58±6 at days 2, 7, and 14, respectively, p<0.001 versus control, Figure 2B, n=7).
Negative_regulation (reduction) of AQP4
9) Confidence 0.55 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2831780 Disease Relevance 0.34 Pain Relevance 0.03
In the present study using the rat ONC model, we have shown for the first time that such injury causes a significant decrease in AQP4 and Kir4.1 protein and mRNA levels in retina, suggesting impaired ion homeostasis and K+ spatial buffering.
Negative_regulation (decrease) of AQP4 in retina associated with injury
10) Confidence 0.55 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2831780 Disease Relevance 0.47 Pain Relevance 0.09
However, AQP4 downregulation may be initially neuroprotective.
Negative_regulation (downregulation) of AQP4
11) Confidence 0.55 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2831780 Disease Relevance 0.63 Pain Relevance 0.09
An imbalanced reduction of AQP4 levels may therefore impair retinal K+ buffering, and uncontrolled increases in [K+]o may induce uncontrolled hyperexcitability and abnormal synchronization of retinal neurons.
Negative_regulation (reduction) of AQP4 in neurons associated with hyperexcitability
12) Confidence 0.55 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2831780 Disease Relevance 0.24 Pain Relevance 0.08
For example, while middle cerebral artery occlusion and hyperosmotic stress induced by intraperitoneal infusion of mannitol increased AQP4 in rodent brain [64,65], hypoxia evoked a marked decrease in AQP4 in astrocytes in vitro, and subsequent re-oxygenation elicited the restoration of the expression of AQP4 to its basal levels [66].
Negative_regulation (decrease) of AQP4 in middle cerebral artery associated with stress, hypoxia and middle cerebral artery infarction
13) Confidence 0.55 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2831780 Disease Relevance 0.76 Pain Relevance 0.07
The loss of AQP4 was evident in the central gray matter, especially in the perivascular lesions where immunoglobulins and complements were deposited, and glial fibrillary acidic protein (GFAP) staining was weak in those lesions.
Negative_regulation (loss) of AQP4 in central gray
14) Confidence 0.55 Published 2006 Journal Tohoku J. Exp. Med. Section Abstract Doc Link 16778375 Disease Relevance 1.62 Pain Relevance 0.39
Loss of aquaporin-4 in active perivascular lesions in neuromyelitis optica: a case report.
Negative_regulation (Loss) of aquaporin-4 associated with neuromyelitis optica
15) Confidence 0.55 Published 2006 Journal Tohoku J. Exp. Med. Section Title Doc Link 16778375 Disease Relevance 1.57 Pain Relevance 0.39
An antibody-mediated pathogenesis for NMO is supported by several observations, including the characteristics of the AQP4 antibodies, the distinct NMO pathology--which includes IgG and complement deposition and loss of AQP4 from spinal cord lesions--and emerging evidence of the beneficial effects of B-cell depletion and plasma exchange.
Negative_regulation (loss) of AQP4 in plasma associated with neuromyelitis optica and spinal cord
16) Confidence 0.44 Published 2008 Journal Nature clinical practice. Neurology Section Abstract Doc Link 18334978 Disease Relevance 1.26 Pain Relevance 0.24
Thus, AQP4 inhibition or antagonism of its signalling, potentially reduce the development of cytotoxic edema by means of reducing cellular water accumulation in the brain.
Negative_regulation (inhibition) of AQP4 in brain associated with edema
17) Confidence 0.43 Published 2010 Journal Cerebrospinal Fluid Res Section Body Doc Link PMC2987763 Disease Relevance 0.72 Pain Relevance 0.03
Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week.
Negative_regulation (decreased) of AQP4 in cortex
18) Confidence 0.43 Published 2010 Journal Cerebrospinal Fluid Res Section Abstract Doc Link PMC2987763 Disease Relevance 0.39 Pain Relevance 0.08
We therefore suggest a biphasic neuroprotective response consisting of down-regulation of AQP4 after two days, corresponding to acutely increased ICP, and up-regulation after two weeks, corresponding to a near-normal ICP phase [15,37-40].
Negative_regulation (regulation) of AQP4
19) Confidence 0.43 Published 2010 Journal Cerebrospinal Fluid Res Section Body Doc Link PMC2987763 Disease Relevance 0.89 Pain Relevance 0.04
Inhibitors of brain glial water channel aquaporin-4 (AQP4) are of potential clinical utility, as they are predicted to modulate brain edema, neuroexcitation and glial scarring.
Negative_regulation (Inhibitors) of aquaporin-4 in brain associated with pressure and volume under development and keloid scars
20) Confidence 0.43 Published 2008 Journal Bioorg. Med. Chem. Section Abstract Doc Link 18572411 Disease Relevance 0.19 Pain Relevance 0.08

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