INT232825

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Context Info
Confidence 0.44
First Reported 2008
Last Reported 2008
Negated 0
Speculated 0
Reported most in Body
Documents 1
Total Number 10
Disease Relevance 6.83
Pain Relevance 0.42

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

structural molecule activity (Krt8) nucleus (Krt8) cytoplasm (Krt8)
Anatomy Link Frequency
liver 1
filament 1
Krt8 (Mus musculus)
Krt8 - G61C (1)
Pain Link Frequency Relevance Heat
fibrosis 80 95.88 Very High Very High Very High
Potency 10 95.16 Very High Very High Very High
Paracetamol 40 79.60 Quite High
Inflammation 30 62.40 Quite High
Bile 30 5.00 Very Low Very Low Very Low
alcohol 30 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Targeted Disruption 140 99.28 Very High Very High Very High
Stress 180 98.24 Very High Very High Very High
Liver Disease 150 97.60 Very High Very High Very High
Chronic Hepatitis 40 97.28 Very High Very High Very High
Disease 170 96.48 Very High Very High Very High
Cirrhosis 80 95.88 Very High Very High Very High
Acute Liver Failure 90 93.16 High High
Aging 20 91.68 High High
Apoptosis 230 88.76 High High
Nash(non-alcoholic Steatohepatitis) 70 87.96 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Major factors that determine MDB formation in vivo are the type of stress (with oxidative stress as a major player), the extent of stress-induced protein misfolding and resulting chaperone, proteasome and autophagy overload, keratin 8 excess, transglutaminase activation with transamidation of keratin 8 and p62 upregulation.



Positive_regulation (upregulation) of keratin 8 associated with stress
1) Confidence 0.44 Published 2008 Journal Histochem Cell Biol Section Abstract Doc Link PMC2386529 Disease Relevance 0.76 Pain Relevance 0.03
The elevated K8/K18 ratio is crucial for MDB formation as shown in K18-knockout and K8 overexpressing animals, who are predisposed to MDB formation already upon short exposure to DDC and even form MDBs spontaneously during aging (Magin et al. 1998; Nakamichi et al. 2005).
Positive_regulation (elevated) of K8 associated with targeted disruption and aging
2) Confidence 0.32 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.71 Pain Relevance 0
The recently established transgenic mouse lines overexpressing the naturally occurring K8 G61C and R340H variants will likely offer valuable insights in this respect (Ku and Omary 2006; Zhou et al., unpublished data).


Positive_regulation (occurring) of K8 G61C (G61C) associated with targeted disruption
3) Confidence 0.32 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.79 Pain Relevance 0.11
Mallory-Denk bodies (MDBs) are protein aggregates consisting of ubiquitinated K8/K18, chaperones and sequestosome1/p62 (p62) as their major constituents.
Positive_regulation (ubiquitinated) of K8
4) Confidence 0.32 Published 2008 Journal Histochem Cell Biol Section Abstract Doc Link PMC2386529 Disease Relevance 1.10 Pain Relevance 0.05
The naturally occurring K8/K18 variants interfere with basic IF properties such as K8/K18 filament assembly and keratin solubility (Ku et al. 2001; Owens et al. 2004; Ku et al. 2007).
Positive_regulation (occurring) of K8 in filament
5) Confidence 0.32 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.81 Pain Relevance 0.12
The large body of evidence from animal studies showing the importance of K8/K18 for liver homeostasis led to a search for keratin mutations in patients with liver diseases.
Positive_regulation (importance) of K8 in liver associated with liver disease
6) Confidence 0.32 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.94 Pain Relevance 0.07
The K8/K18 within MDBs exhibit increased ?
Positive_regulation (increased) of K8
7) Confidence 0.30 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.09 Pain Relevance 0
Griseofulvin/DDC feeding leads to rapid induction of K8/K18 expression with disproportional K8 > K18 levels (Denk et al. 2000).
Positive_regulation (induction) of K8
8) Confidence 0.28 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.72 Pain Relevance 0
Major factors that determine MDB formation in vivo are the type of stress (with oxidative stress as a major player), the extent of stress-induced protein misfolding and resulting chaperone, proteasome and autophagy overload, keratin 8 excess, transglutaminase activation with transamidation of keratin 8 and p62 upregulation.



Positive_regulation (excess) of keratin 8 associated with stress
9) Confidence 0.26 Published 2008 Journal Histochem Cell Biol Section Abstract Doc Link PMC2386529 Disease Relevance 0.78 Pain Relevance 0.04
Alternatively, K8 hyperphosphorylation may induce MDB formation through inhibition of K8 degradation, which results in increased K8/K18 ratio (Ku and Omary 2000).
Positive_regulation (increased) of K8
10) Confidence 0.11 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.13 Pain Relevance 0

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