INT110038

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Context Info
Confidence 0.23
First Reported 2003
Last Reported 2010
Negated 0
Speculated 3
Reported most in Body
Documents 26
Total Number 30
Disease Relevance 17.41
Pain Relevance 2.20

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

cytosol (Aco1) mitochondrion (Aco1) lyase activity (Aco1)
Golgi apparatus (Aco1) endoplasmic reticulum (Aco1) RNA binding (Aco1)
Anatomy Link Frequency
neuronal 5
neurons 4
astrocytes 2
liver 1
midbrain 1
Aco1 (Mus musculus)
Pain Link Frequency Relevance Heat
cINOD 10 100.00 Very High Very High Very High
Substantia nigra 26 99.52 Very High Very High Very High
midbrain 468 98.88 Very High Very High Very High
addiction 26 91.80 High High
ischemia 27 86.80 High High
Inflammation 33 84.24 Quite High
Pain 26 5.00 Very Low Very Low Very Low
tolerance 7 5.00 Very Low Very Low Very Low
Paracetamol 3 5.00 Very Low Very Low Very Low
Analgesic 2 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Death 1539 99.70 Very High Very High Very High
Parkinson's Disease 286 99.48 Very High Very High Very High
Neurodegenerative Disease 104 98.44 Very High Very High Very High
Stress 412 97.90 Very High Very High Very High
Drug Induced Neurotoxicity 208 96.68 Very High Very High Very High
Aging 63 92.76 High High
Injury 94 91.92 High High
Disease 238 91.04 High High
Toxicity 107 90.04 High High
Supranuclear Palsy 26 88.80 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Consistent with our previous work [17] aconitase activity was decreased after 2–3 hrs of PQ2+ incubation while the activity of fumarase, a control enzyme which lacks an oxidation sensitive Fe-S center, remained unchanged suggesting a role for oxidative stress in the mechanism of aconitase inactivation (Fig. 1a).
Negative_regulation (decreased) of aconitase associated with stress
1) Confidence 0.23 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.44 Pain Relevance 0.12
Collectively, these reasons may render midbrain neurons more sensitive to neuronal death via oxidative inactivation of m-aconitase.
Negative_regulation (inactivation) of m-aconitase in neuronal associated with midbrain and death
2) Confidence 0.23 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 1.17 Pain Relevance 0.17
Several reasons may underlie the greater sensitivity of primary midbrain neurons, as opposed to astrocytes, to death via oxidative inactivation of m-aconitase.
Negative_regulation (inactivation) of m-aconitase in neurons associated with midbrain and death
3) Confidence 0.23 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.61 Pain Relevance 0.13
Together these studies demonstrate increased H2O2 production and mitochondrial iron accumulation following oxidative inactivation of aconitase at times preceding cell death.


Negative_regulation (inactivation) of aconitase associated with death
4) Confidence 0.20 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.22 Pain Relevance 0.08
Intramitochondrial Fe2+ in conjunction with H2O2 via the Fenton reaction may be the chief mediator of neuronal death following oxidative inactivation of endogenous m-aconitase residing in both neurons and astrocytes.
Negative_regulation (inactivation) of m-aconitase in astrocytes associated with death
5) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.62 Pain Relevance 0
The goal of this study was to determine if oxidative inactivation of mitochondrial aconitase (m-aconitase) resulted in the release of redox-active iron (Fe2+) and hydrogen peroxide (H2O2) and whether this contributes to cell death.


Negative_regulation (inactivation) of aconitase associated with death
6) Confidence 0.17 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2738973 Disease Relevance 0.49 Pain Relevance 0
Indeed several neurodegenerative diseases in which oxidative stress has been implicated, as well as in vivo and in vitro models of these disorders collectively demonstrate decreased aconitase activity [1], [14], [15], [16], [17], [18], [19], [20].
Negative_regulation (decreased) of aconitase associated with stress and neurodegenerative disease
7) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.32 Pain Relevance 0
Finally, neurons showed greater vulnerability to oxidative inactivation of m-aconitase.
Negative_regulation (inactivation) of m-aconitase in neurons
8) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 1.23 Pain Relevance 0.15
H2O2 production, mitochondrial Fe2+ accumulation and cell death occur following oxidative inactivation of aconitase
Negative_regulation (inactivation) of aconitase associated with death
9) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.43 Pain Relevance 0.11
However, whether oxidative inactivation of m-aconitase is a source of Fe2+ and H2O2 in intact neuronal cells and whether it contributes to neurotoxicity remains unknown.
Spec (whether) Negative_regulation (inactivation) of m-aconitase in neuronal associated with drug induced neurotoxicity
10) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.76 Pain Relevance 0.08
Importantly, the time-course of cell death confirms that H2O2 formation and Fe2+ release occur hours prior to cell death, suggesting that oxidative inactivation of m-aconitase contributes to cell death in primary midbrain cultures.


Negative_regulation (inactivation) of m-aconitase in midbrain associated with midbrain and death
11) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 1.03 Pain Relevance 0.05
The goal of this study was to determine if oxidative inactivation of mitochondrial aconitase (m-aconitase) resulted in the release of redox-active iron (Fe2+) and hydrogen peroxide (H2O2) and whether this contributes to cell death.


Negative_regulation (inactivation) of m-aconitase associated with death
12) Confidence 0.17 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2738973 Disease Relevance 0.50 Pain Relevance 0
To verify whether oxidative inactivation of m-aconitase played a role in releasing Fe2+ in addition to H2O2, m-aconitase was overexpressed with AdAcon and levels of Fe2+ were measured.
Spec (whether) Negative_regulation (inactivation) of m-aconitase
13) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0 Pain Relevance 0.13
Evidence of .OH formation in cell free systems, presumably via the release of Fenton reactants by oxidative inactivation of m-aconitase was provided by Vasquez-Vivar et al. (2000).
Negative_regulation (inactivation) of m-aconitase
14) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.32 Pain Relevance 0
Of note, the use of PQ2+ as a toxicant was particularly advantageous in our model because in contrast to neuron-specific toxicants such as MPP+, PQ2+ is capable of inactivating m-aconitase in both mixed neuronal/glial cultures and near pure astrocytic cultures [30].
Negative_regulation (inactivating) of m-aconitase in neuron
15) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.58 Pain Relevance 0.05
Decreased aconitase activity is observed in various human neurodegenerative diseases associated with mitochondrial oxidative stress e.g.
Negative_regulation (Decreased) of aconitase associated with stress and neurodegenerative disease
16) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 1.45 Pain Relevance 0.15
Since AdAcon was primarily transduced in astrocytes and cell death was evident in neurons, but not astrocytes, it suggests that oxidative inactivation of astrocytic m-aconitase results in H2O2 release which kills neurons in a paracrine manner.
Negative_regulation (inactivation) of m-aconitase in astrocytes associated with death
17) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.70 Pain Relevance 0
Together these studies suggest that inactivation of m-aconitase increases mitochondrial iron.


Negative_regulation (inactivation) of m-aconitase
18) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.37 Pain Relevance 0
The goal of this study was to test the hypothesis that oxidative inactivation of m-aconitase and consequent release of the Fenton reactants H2O2 and Fe2+ contributes to neuronal death.
Negative_regulation (inactivation) of m-aconitase in neuronal associated with death
19) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.72 Pain Relevance 0.09
We therefore asked whether oxidative inactivation of m-aconitase resulted in mitochondrial dysfunction and cell death 18 hrs after PQ2+ incubation in AdGFP vs.
Spec (whether) Negative_regulation (inactivation) of m-aconitase associated with parkinson's disease and death
20) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2738973 Disease Relevance 0.51 Pain Relevance 0

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