INT215261

Context Info Confidence 0.30 First Reported 2007 Last Reported 2008 Negated 0 Speculated 0 Reported most in Body Documents 6 Total Number 8 Disease Relevance 3.51 Pain Relevance 0.74

cell proliferation (Ncf1) cytosol (Ncf1) Golgi apparatus (Ncf1) plasma membrane (Ncf1) cytoplasm (Ncf1)

Anatomy Link Frequency plasma 4 microglial cells 2 Ncf1 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 212 98.02 narcan 10 92.40 opioid receptor 10 86.16 Enkephalin 5 85.52 Inflammatory response 10 75.32 midbrain 20 65.84 rheumatoid arthritis 10 42.24 cINOD 3 34.04 Inflammatory mediators 35 31.88 Substantia nigra 17 5.00

Disease Link Frequency Relevance Heat INFLAMMATION 260 98.02 Parkinson's Disease 113 96.40 Drug Induced Neurotoxicity 131 95.12 Disease 121 90.32 Death 42 85.44 Necrosis 16 82.92 Cancer 19 82.56 Toxicity 33 71.28 Stress 15 62.44 Neurodegenerative Disease 35 57.04

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Presently the molecular mechanisms by which SN leads to the inhibition of p47phox translocation are under investigation.

Negative_regulation (inhibition) of Localization (translocation) of p47phox

1) Confidence 0.30 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC2064906 Disease Relevance 0.41 Pain Relevance 0.12

Therefore, one mechanism by which SN inhibits superoxide production in microglial cells is through inhibition of p47phox translocation to the cell membrane following LPS stimulation.

Negative_regulation (inhibition) of Localization (translocation) of p47phox in microglial cells

2) Confidence 0.22 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC2064906 Disease Relevance 0.30 Pain Relevance 0.11

In summary, this study is the first report indicating that SN is a potent anti-inflammatory and neuroprotective agent that acts through inhibition of microglial PHOX-generated superoxide by inhibiting the translocation of p47phox to the plasma membrane.

Negative_regulation (inhibiting) of Localization (translocation) of p47phox in plasma associated with inflammation

3) Confidence 0.22 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC2064906 Disease Relevance 0.92 Pain Relevance 0.20

However, the addition of 10-14 M SN significantly prevented this LPS-induced p47phox translocation (Fig. 5, panel V and VI).

Negative_regulation (prevented) of Localization (translocation) of p47phox

4) Confidence 0.22 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC2064906 Disease Relevance 0 Pain Relevance 0

We found that the translocation of the p47phox subunit from the cytosol to the plasma membrane following LPS stimulation was inhibited by SN.

Negative_regulation (inhibited) of Localization (translocation) of p47phox in plasma

5) Confidence 0.19 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC2064906 Disease Relevance 0.39 Pain Relevance 0.19

A critical role for PHOX in FLZ-elicited neuroprotection was further supported by the findings that 1) FLZ's protective effect was reduced in cultures from PHOX-/- mice, and 2) FLZ inhibited LPS-induced translocation of the cytosolic subunit of p47PHOX to the membrane and thus inhibited the activation of PHOX.

Negative_regulation (inhibited) of Localization (translocation) of p47PHOX

6) Confidence 0.19 Published 2008 Journal J Neuroinflammation Section Abstract Doc Link PMC2413210 Disease Relevance 0.79 Pain Relevance 0.11

Western blot analysis from this study revealed that FLZ inhibited LPS-induced p47phox translocation from cytosol to membrane.

Negative_regulation (inhibited) of Localization (translocation) of p47phox

7) Confidence 0.19 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2413210 Disease Relevance 0.25 Pain Relevance 0

Thus, this result further proves that FLZ-mediated inhibition of superoxide production by LPS is mediated through suppression of p47phox membrane translocation; that is, activation of PHOX.

Negative_regulation (suppression) of Localization (translocation) of p47phox

8) Confidence 0.19 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2413210 Disease Relevance 0.45 Pain Relevance 0

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