INT123816

Context Info Confidence 0.50 First Reported 2005 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 9 Total Number 10 Disease Relevance 6.64 Pain Relevance 1.04

nucleoplasm (Parp1) nuclear envelope (Parp1) nucleolus (Parp1) nucleus (Parp1) protein complex (Parp1) transcription factor binding (Parp1)

Anatomy Link Frequency cleavage 3 MCF-7 2 lung 2 MDA-MB-231 2 liver 1 Parp1 (Mus musculus)

Pain Link Frequency Relevance Heat carrageenan induced 2 100.00 Paracetamol 10 99.68 Inflammatory response 8 87.16 iatrogenic 1 83.88 Inflammation 103 78.96 agonist 34 75.00 imagery 34 65.84 Inflammatory mediators 3 64.40 cINOD 5 61.92 COX-2 inhibitor 20 5.00

Disease Link Frequency Relevance Heat Apoptosis 241 100.00 Injury 12 99.96 Cancer 392 99.78 Necrosis 20 98.36 Death 54 97.32 Overdose 4 94.76 Lymphatic System Cancer 16 87.20 INFLAMMATION 109 86.80 Hepatotoxicity 1 85.04 Lung Injury 108 84.72

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Pathophysiological role of poly(ADP-ribose) polymerase (PARP) activation during acetaminophen-induced liver cell necrosis in mice.

Positive_regulation (activation) of in poly Gene_expression (role) of PARP in liver associated with necrosis and paracetamol

1) Confidence 0.50 Published 2005 Journal Toxicol. Sci. Section Title Doc Link 15601672 Disease Relevance 0.50 Pain Relevance 0.56

PARP-1 is needed for optimal activation of ATM

Positive_regulation (activation) of Gene_expression (needed) of PARP-1

2) Confidence 0.50 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.06 Pain Relevance 0

However, under conditions of severe DNA injury, overactivation of PARP severely depletes the intracellular stores of NAD+, slowing the rate of glycolysis, mitochondrial respiration, and high-energy phosphate generation, ultimately leading to cell death via the necrotic pathway [7].

Positive_regulation (overactivation) of Gene_expression (overactivation) of PARP associated with injury and death

3) Confidence 0.48 Published 2008 Journal Crit Care Section Body Doc Link PMC2575597 Disease Relevance 1.22 Pain Relevance 0.14

The biological consequence of this interaction is a diminished activation of ATM-kinase in the absence of PARP-1.

Positive_regulation (activation) of Neg (absence) Gene_expression (absence) of PARP-1

4) Confidence 0.46 Published 2007 Journal BMC Mol Biol Section Body Doc Link PMC1868035 Disease Relevance 0.07 Pain Relevance 0

Both caspase-3 activation and PARP-1 cleavage as early and late markers of apoptosis, respectively, increased directly as a function of chemotherapy dose.

Positive_regulation (increased) of Gene_expression (cleavage) of PARP-1 in cleavage associated with apoptosis

5) Confidence 0.33 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2645692 Disease Relevance 0.89 Pain Relevance 0

Immunohistochemical analysis of EL4 tumor caspase-3 activation and PARP-1 cleavage and immunofluorescence analysis of in vivo tumor binding of DAB4

Positive_regulation (activation) of in EL4 Gene_expression (cleavage) of PARP-1 in cleavage associated with cancer

6) Confidence 0.33 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2645692 Disease Relevance 1.50 Pain Relevance 0.03

Effects of T0901317 on carrageenan-induced nitrotyrosine formation, lipid peroxidation and PARP activation

Positive_regulation (induced) of Gene_expression (activation) of PARP

7) Confidence 0.26 Published 2010 Journal Respir Res Section Body Doc Link PMC2836283 Disease Relevance 0.15 Pain Relevance 0

Furthermore, carrageenan induced the expression of iNOS, nitrotyrosine and PARP, as well as induced apoptosis (TUNEL staining and Bax and Bcl-2 expression) in the lung tissues.

Positive_regulation (induced) of Gene_expression (expression) of PARP in lung associated with apoptosis and carrageenan induced

8) Confidence 0.24 Published 2010 Journal Respir Res Section Abstract Doc Link PMC2836283 Disease Relevance 0.68 Pain Relevance 0.24

The increase in PARP-1 cleavage in MCF-7 cells, which have a decreased level of PPAR?

Positive_regulation (increase) of Gene_expression (cleavage) of PARP-1 in MCF-7

9) Confidence 0.13 Published 2008 Journal Mol Cancer Section Body Doc Link PMC2614423 Disease Relevance 1.17 Pain Relevance 0

Celecoxib treatment led to the disappearance of uncleaved PARP (116 kDa) in both cell lines; it also led to the appearance of cleaved PARP (89 kDa) in MDA-MB-435-E1A cells and the appearance of cleaved PARP expression in MDA-MB-231-E1A cells (Figure 3B).

Positive_regulation (cleaved) of Gene_expression (expression) of PARP in MDA-MB-231

10) Confidence 0.06 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC2206712 Disease Relevance 0.40 Pain Relevance 0.06

General Comments

This test has worked.