INT224369

Context Info Confidence 0.42 First Reported 2007 Last Reported 2010 Negated 2 Speculated 0 Reported most in Body Documents 43 Total Number 44 Disease Relevance 40.57 Pain Relevance 3.86

extracellular space (Ager) plasma membrane (Ager) cytoplasm (Ager)

Anatomy Link Frequency hearts 5 endothelial cells 1 neurons 1 tail 1 nucleus 1 Ager (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 1549 99.84 Abeta 312 99.84 psoriasis 26 99.04 Inflammatory response 84 98.68 cytokine 391 92.48 rheumatoid arthritis 33 91.80 Arthritis 52 88.68 Osteoarthritis 52 87.96 ischemia 134 85.20 fibrosis 104 84.56

Disease Link Frequency Relevance Heat Diabetes Mellitus 1794 100.00 Targeted Disruption 670 100.00 Injury 381 100.00 Prostate Cancer 26 99.86 INFLAMMATION 1659 99.84 Myocardial Infarction 46 99.84 Stress 433 99.76 Skin Cancer 26 99.56 Hypersensitivity 85 99.28 Disease 396 99.08

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Specificity of the antibody was demonstrated by binding to RAGE on the cell surface, direct binding to sRAGE, and immunohistochemistry (manuscript in preparation).

RAGE Binding (binding) of

1) Confidence 0.42 Published 2007 Journal Crit Care Section Body Doc Link PMC2246216 Disease Relevance 0.53 Pain Relevance 0

RAGE is a pattern-recognition receptor that binds diverse classes of endogenous molecules.

RAGE Binding (binds) of

2) Confidence 0.42 Published 2007 Journal Crit Care Section Body Doc Link PMC2246216 Disease Relevance 1.17 Pain Relevance 0.20

Specificity of the antibody was demonstrated by binding to RAGE on the cell surface, direct binding to sRAGE, and immunohistochemistry (manuscript in preparation).

sRAGE Binding (binding) of

3) Confidence 0.42 Published 2007 Journal Crit Care Section Body Doc Link PMC2246216 Disease Relevance 0.53 Pain Relevance 0

A major way in which AGEs exert their cellular effects is by ligation of the multiligand receptor for AGE (RAGE) (10–13).

RAGE Binding (ligation) of

4) Confidence 0.38 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 1.09 Pain Relevance 0.16

Equivalent amounts of total protein from each sample were analyzed by electrophoresis on a NuPAGE 4% to 12% Bis-Tris gel (Invitrogen Corporation, Carlsbad, CA, USA) and detected with immunodetection with the RAGE mAb or actin antibody and a horseradish peroxidase-conjugated anti-donkey antibody using standard protocols.

RAGE mAb Binding (immunodetection) of

5) Confidence 0.37 Published 2007 Journal Crit Care Section Body Doc Link PMC2246216 Disease Relevance 0.25 Pain Relevance 0

This mAb is a high-affinity rat-derived anti-mouse RAGE antibody with a binding affinity of 0.3 nM for murine dimeric RAGE and binds to the N-terminal region of RAGE.

RAGE Binding (binds) of

6) Confidence 0.32 Published 2007 Journal Crit Care Section Body Doc Link PMC2246216 Disease Relevance 0.58 Pain Relevance 0

Specificity of the antibody was demonstrated by binding to RAGE on the cell surface, direct binding to sRAGE, and immunohistochemistry (manuscript in preparation).

RAGE Binding (binding) of

7) Confidence 0.31 Published 2007 Journal Crit Care Section Body Doc Link PMC2246216 Disease Relevance 0.54 Pain Relevance 0

This mAb is a high-affinity rat-derived anti-mouse RAGE antibody with a binding affinity of 0.3 nM for murine dimeric RAGE and binds to the N-terminal region of RAGE.

RAGE Binding (binds) of

8) Confidence 0.31 Published 2007 Journal Crit Care Section Body Doc Link PMC2246216 Disease Relevance 0.59 Pain Relevance 0

Immunostaining with anti-RAGE IgG revealed that RAGE expression in the Tg mouse heart was localized to endothelial cells and not to cardiomyocytes (Fig. 6A).

anti-RAGE Binding (Immunostaining) of in heart associated with targeted disruption

9) Confidence 0.29 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 1.63 Pain Relevance 0.04

In conclusion, these studies definitively link RAGE to myocardial ischemic injury and dysfunction in the diabetic heart.

RAGE Binding (link) of in heart associated with diabetes mellitus and myocardial infarction

10) Confidence 0.29 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 1.96 Pain Relevance 0

Interestingly, after I/R, CML levels were significantly greater in diabetic WT hearts in comparison with diabetic RAGE-KO, Tg DN PPET RAGE, and Tg DN MSR RAGE hearts (Table 2).

RAGE-KO Binding (comparison) of in hearts associated with targeted disruption, myeloid leukemia and diabetes mellitus

11) Confidence 0.29 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 3.35 Pain Relevance 0

Interestingly, after I/R, CML levels were significantly greater in diabetic WT hearts in comparison with diabetic RAGE-KO, Tg DN PPET RAGE, and Tg DN MSR RAGE hearts (Table 2).

RAGE Binding (comparison) of in hearts associated with targeted disruption, myeloid leukemia and diabetes mellitus

12) Confidence 0.29 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 3.42 Pain Relevance 0

We observed that in diabetic RAGE KO, Tg DN PPET RAGE, and Tg DN MSR RAGE mice hearts, protection from injury due to I/R was also associated with reductions in caspase-3 activation and cytochrome c release.

RAGE Binding (associated) of in hearts associated with targeted disruption, diabetes mellitus and injury

13) Confidence 0.29 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 2.26 Pain Relevance 0

Transgenic (Tg) DN MSR RAGE and Tg DN PPET RAGE mice were prepared and characterized as previously described (20,22).

RAGE Binding (characterized) of associated with targeted disruption

14) Confidence 0.29 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 0.67 Pain Relevance 0

We extended our studies to murine models, wherein genetic modification of RAGE would complement pharmacological blockade of ligand-RAGE interaction (sRAGE).

sRAGE Binding (interaction) of

15) Confidence 0.28 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 1.34 Pain Relevance 0

We extended our studies to murine models, wherein genetic modification of RAGE would complement pharmacological blockade of ligand-RAGE interaction (sRAGE).

RAGE Binding (interaction) of

16) Confidence 0.28 Published 2008 Journal Diabetes Section Body Doc Link PMC2453611 Disease Relevance 1.34 Pain Relevance 0

The binding of RAGE by AGEs is capable of mediating inflammatory responses and oxidative stress and leads to diabetic vascular complications [136, 137].

RAGE Binding (binding) of associated with diabetic angiopathy, stress and inflammatory response

17) Confidence 0.13 Published 2010 Journal The Open Biochemistry Journal Section Body Doc Link PMC2864432 Disease Relevance 1.14 Pain Relevance 0.07

AGE products bind to RAGE, which is present in neurons and binds to amyloidogenic APP derivative A?

RAGE Binding (binds) of in neurons

18) Confidence 0.09 Published 2010 Journal The Open Biochemistry Journal Section Body Doc Link PMC2864432 Disease Relevance 1.21 Pain Relevance 0.12

It binds to the RAGE C1 and C2 domains instead of the V domain [49].

RAGE C1 Binding (binds) of

19) Confidence 0.01 Published 2009 Journal J Transl Med Section Body Doc Link PMC2666642 Disease Relevance 1.03 Pain Relevance 0.17

It can also bind to RAGE expressed on endothelial cells, signaling through the NF-?

RAGE Binding (bind) of in endothelial cells

20) Confidence 0.01 Published 2009 Journal J Transl Med Section Body Doc Link PMC2666642 Disease Relevance 0.97 Pain Relevance 0.17

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