INT159946

Context Info Confidence 0.77 First Reported 2009 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 23 Total Number 27 Disease Relevance 15.33 Pain Relevance 7.49

Anatomy Link Frequency brain 7 AMs 4 poly 1 liver 1 F4/80 1 Mat1a (Mus musculus)

Pain Link Frequency Relevance Heat agonist 33 99.74 substance P 56 99.58 Paracetamol 79 99.40 c fibre 4 98.42 Inflammation 49 90.48 adenocard 30 88.32 Hippocampus 30 80.48 Neurotransmitter 15 77.20 cytokine 18 54.12 isoflurane 9 18.32

Disease Link Frequency Relevance Heat Neuroblastoma 30 99.60 Toxicity 20 99.60 Aging 285 99.20 Disease 642 99.00 Increased Venous Pressure Under Development 30 98.48 Coronavirus Infection 84 97.68 Severe Acute Respiratory Syndrome 114 97.52 Cognitive Disorder 105 97.24 Liver Failure 4 97.08 Hepatotoxicity 2 96.24

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Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Temporal study of acetaminophen (APAP) and S-adenosyl-L-methionine (SAMe) effects on subcellular hepatic SAMe levels and methionine adenosyltransferase (MAT) expression and activity.

Gene_expression (expression) of MAT associated with paracetamol

1) Confidence 0.77 Published 2010 Journal Toxicol. Appl. Pharmacol. Section Title Doc Link 20450926 Disease Relevance 0.48 Pain Relevance 1.09

Studies further examined MAT expression and activity in response to APAP toxicity.

Spec (examined) Gene_expression (expression) of MAT associated with toxicity and paracetamol

2) Confidence 0.77 Published 2010 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 20450926 Disease Relevance 0.51 Pain Relevance 1.11

MAT expression was examined by Western blot.

Spec (examined) Gene_expression (expression) of MAT

3) Confidence 0.77 Published 2010 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 20450926 Disease Relevance 0.46 Pain Relevance 1.45

In addition they measured the synthesis of AdoMet by adenosyl transferase and AdoMet utilization by COMT, and concluded that the decrease in AdoMet levels was a consequence of increased utilization during aging.

Gene_expression (synthesis) of AdoMet associated with aging

4) Confidence 0.67 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.67 Pain Relevance 0.03

SAMe is synthesized in cells through the action of methionine adenosyltransferase (MAT).

Gene_expression (synthesized) of MAT

5) Confidence 0.67 Published 2010 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 20450926 Disease Relevance 0.46 Pain Relevance 0.97

It could be suggested that AdoMet levels in the brain tissue of the APP/PS1 mice, used in this study, do not decrease during aging because of less demand caused by neurodegeneration.

Gene_expression (levels) of AdoMet in brain associated with aging

6) Confidence 0.59 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.65 Pain Relevance 0.04

In addition they measured the synthesis of AdoMet by adenosyl transferase and AdoMet utilization by COMT, and concluded that the decrease in AdoMet levels was a consequence of increased utilization during aging.

Gene_expression (utilization) of AdoMet associated with aging

7) Confidence 0.58 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.63 Pain Relevance 0.03

The finding that AdoMet levels do not differ between the genotypes in (young) 8-month-old mice, but do differ in (older) 15-month-old APP/PS1 mice compared to their wild type littermates, suggests that alterations in AdoMet are a consequence of AD pathology rather than a cause, and it could be suggested that it is the result of neurodegeneration during aging (Fig. 2).

Gene_expression (levels) of AdoMet associated with aging and disease

8) Confidence 0.51 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.66 Pain Relevance 0

AdoMet and AdoHcy might also influence AD like pathology and vascular health [16] and it could be hypothesized that the above-mentioned nutritional components may influence and AdoMet and AdoHcy levels as well.

Gene_expression (levels) of AdoMet associated with disease

9) Confidence 0.51 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.73 Pain Relevance 0.04

AdoMet is a biological methyl donor and is a product of the conversion of methionine and ATP.

Gene_expression (product) of AdoMet

10) Confidence 0.51 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 1.26 Pain Relevance 0.07

Stramentinoli et al. found decreased AdoMet levels in brain tissue of aging rats [33].

Gene_expression (levels) of AdoMet in brain associated with aging

11) Confidence 0.51 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.66 Pain Relevance 0

This is the first study describing AdoMet and AdoHcy levels in brain tissue of aging mice.

Gene_expression (levels) of AdoMet in brain associated with aging

12) Confidence 0.51 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.60 Pain Relevance 0

However, because of a lack of brain tissue we only measured AdoMet and AdoHcy levels in this experiment.

Gene_expression (levels) of AdoMet in brain

13) Confidence 0.51 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.53 Pain Relevance 0

For example, AdoMet administration in human neuroblastoma cells down regulates PS1 gene expression and A?

Gene_expression (administration) of AdoMet associated with neuroblastoma

14) Confidence 0.51 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.62 Pain Relevance 0.12

The finding that cholesterol- or DHA-containing diets do not alter AdoMet or AdoHcy levels in brain tissue of either wild type or APP/PS1 mice, but in contrast do have effects on AD pathology and cerebral hemodynamics [7, 15, 29], suggests that cholesterol- or DHA-containing diets do not influence cerebral hemodynamics or AD pathology via the methylation cycle.

Gene_expression (levels) of AdoMet in brain associated with disease

15) Confidence 0.46 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.64 Pain Relevance 0

Neither a cholesterol- nor a DHA-containing diet did alter AdoMet or AdoHcy levels in brain tissue of 8- and 15-month-old APP/PS1 and wild-type mice as compared to the standard diet (data not shown).

Gene_expression (levels) of AdoMet in brain

16) Confidence 0.46 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.63 Pain Relevance 0

The finding that AdoMet levels in APP/PS1 mice are not decreased during aging (in contrast to wild-type mice), is probably related to less demand due to neurodegeneration.

Gene_expression (levels) of AdoMet associated with aging

17) Confidence 0.46 Published 2009 Journal Neurol Sci Section Abstract Doc Link PMC2746292 Disease Relevance 0.66 Pain Relevance 0

This could have explained the high-AdoMet levels; however, the AdoMet levels in the 8-month-old APP/PS1 mice in our study, should have been increased compared to 8-month-old wild types, and that was not the case.

Gene_expression (levels) of AdoMet

18) Confidence 0.46 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.45 Pain Relevance 0.03

In addition, we showed that cholesterol-containing, or DHA-enriched diets did not affect AdoMet or AdoHcy levels in brain tissue of APP/PS1 and wild-type mice.

Gene_expression (levels) of AdoMet in brain

19) Confidence 0.46 Published 2009 Journal Neurol Sci Section Body Doc Link PMC2746292 Disease Relevance 0.59 Pain Relevance 0

This work was designed to see whether combination use of Gly and Mat could offer better liver protective and anti-hepatocarcinogenic effects than Gly or Mat alone, and whether it could reduce the adverse effects of Gly alone by acetaminophen-induced hepatotoxicity, diethylnitrosamine-induced hepatocarcinogenesis, induction of immunosuppression, albumen-induced swelling of rat hind paws.

Gene_expression (effects) of Mat in liver associated with pressure and volume under development, paracetamol and hepatotoxicity

20) Confidence 0.34 Published 2009 Journal Chem. Biol. Interact. Section Abstract Doc Link 19426721 Disease Relevance 0.35 Pain Relevance 0.24

General Comments

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