INT109950

Context Info Confidence 0.37 First Reported 2003 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 7 Total Number 7 Disease Relevance 4.06 Pain Relevance 1.97

transport (Pitpnm1) lipid particle (Pitpnm1) Golgi apparatus (Pitpnm1) endoplasmic reticulum (Pitpnm1) intracellular (Pitpnm1) cytoplasm (Pitpnm1)

Anatomy Link Frequency hepatocytes 2 Pitpnm1 (Mus musculus)

Pain Link Frequency Relevance Heat Paracetamol 33 98.16 adenocard 1 87.64 Quantitative sensory testing 32 82.52 Inflammation 1 75.00 cINOD 2 50.84 fifth nerve 3 50.00 aspirin 1 45.36 Pain 15 5.00 Pain threshold 4 5.00 Paresthesia 2 5.00

Disease Link Frequency Relevance Heat Stress 6 99.96 Toxicity 8 99.76 Apoptosis 21 99.50 Death 7 98.48 Necrosis 8 97.12 Cancer 2 97.04 Injury 9 93.96 Parkinson's Disease 2 83.96 Overdose 2 79.40 Hepatocellular Cancer 4 75.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

METHODS: Male CD-1 mice were given intraperitoneally acetaminophen (350 mg/kg) without or with cyclosporin A (50 mg/kg), a specific inhibitor of MPT.

Negative_regulation (inhibitor) of MPT

1) Confidence 0.37 Published 2005 Journal J. Hepatol. Section Body Doc Link 15629515 Disease Relevance 0.09 Pain Relevance 0

In the presence of fructose plus glycine, CsA decreased apoptosis and delayed but did not prevent the MPT.

Negative_regulation (prevent) of MPT associated with apoptosis

2) Confidence 0.36 Published 2004 Journal Hepatology Section Abstract Doc Link 15486922 Disease Relevance 0.48 Pain Relevance 0.66

The oxidative phase occurs with increased oxidative stress, loss of mitochondrial membrane potential, MPT, and toxicity.

Negative_regulation (loss) of MPT associated with stress and toxicity

3) Confidence 0.35 Published 2005 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 15466245 Disease Relevance 0.78 Pain Relevance 0.44

Acetaminophen (10 micromol/L) induced necrotic killing in approximately 50% of hepatocytes after 6 h and cyclosporin A (CsA), MPT inhibitor, temporarily decreased necrotic killing after 6 h, but cytoprotection was lost after 16 h.

Negative_regulation (inhibitor) of MPT in hepatocytes associated with paracetamol

4) Confidence 0.34 Published 2007 Journal J. Gastroenterol. Hepatol. Section Abstract Doc Link 17567465 Disease Relevance 0.71 Pain Relevance 0.71

In necrotic killing models to rat hepatocytes, salicylate (1 mM) enhanced calcium ionophore (Br-A23187)- and tert-butylhydroperoxide (t-BuOOH)-induced cell death, which was blocked or delayed by cyclosporin A (CsA, 2 microM), a specific inhibitor of the MPT.

Negative_regulation (inhibitor) of MPT in hepatocytes associated with death

5) Confidence 0.05 Published 2003 Journal Toxicol. Sci. Section Abstract Doc Link 12700412 Disease Relevance 1.27 Pain Relevance 0

MPT decreased only within the first 4 weeks.

Negative_regulation (decreased) of MPT

6) Confidence 0.02 Published 2010 Journal Head Face Med Section Body Doc Link PMC2984556 Disease Relevance 0 Pain Relevance 0.08

Coincubation with either cyclosporin A (an MPT inhibitor) or the combination of fructose-1,6-diphosphate (a glycolysis substrate) and oligomycin (an ATPase inhibitor) prevented the decrease in DeltaPsim, ATP depletion, and cell death.

Negative_regulation (inhibitor) of MPT associated with death

7) Confidence 0.00 Published 2006 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 16617166 Disease Relevance 0.73 Pain Relevance 0.09

General Comments

This test has worked.