Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1)

Yamaguchi, Kiyoshi; Whitlock, Nichelle C.; Liggett, Jason L.; Legendre, Alfred M.; Fry, Michael M.; Baek, Seung Joon

doi:10.1016/j.tvjl.2006.12.001

Cited by 10 publications

(14 citation statements)

References 32 publications

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“…These results strongly correlate with the effects of our test drugs on ulcer repair, suggesting an involvement of NAG-1-dependent mechanisms in the ulcer delaying effects of indomethacin, DFU, or SC-560. Consistent with this contention, various COX inhibitors, including indomethacin and SC-560, were found to enhance NAG-1 expression in cancer cell lines, whereas celecoxib was without effect (Baek and Eling, 2006;Yamaguchi et al, 2008).…”

Section: Nsaid-activated Gene and Gastric Ulcer Healing 147supporting

confidence: 55%

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Plays a Role in the Impairing Effects of Cyclooxygenase Inhibitors on Gastric Ulcer Healing

Colucci¹,

Antonioli²,

Bernardini³

et al. 2012

J Pharmacol Exp Ther

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Nonsteroidal anti-inflammatory drugs (NSAIDs) can impair gastric ulcer healing. This study investigates the involvement of NSAIDactivated gene-1 (NAG-1) in ulcer repair impairment by cyclooxygenase (COX) inhibitors. Gastric ulcers were induced in rats by acetic acid. Four days later, animals received daily intragastric indomethacin (nonselective COX-1/COX-2 inhibitor; 1 mg/kg), 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560) (selective COX-1 inhibitor; 2.5 mg/kg), (5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl) phenyl-2(5H)-furanone (DFU) (selective COX-2 inhibitor; 5 mg/kg), celecoxib (selective COX-2 inhibitor; 1 mg/kg), and valdecoxib (selective COX-2 inhibitor; 1 mg/kg), for 1, 3, or 7 days. Ulcerated tissues were processed to assess: 1) COX-1, COX-2, NAG-1, proliferating cell nuclear antigen (PCNA), and activated caspase-3 expression; 2) ulcer area; and 3) prostaglandin E 2 (PGE 2 ) levels. COX-1 expression in ulcerated tissues was decreased, whereas COX-2 expression was enhanced. Ulcer healing was delayed by indomethacin, DFU, and SC-560, but not by celecoxib and valdecoxib. Ulcer PGE 2 levels were decreased by SC-560, DFU, celecoxib, valdecoxib, and indomethacin. NAG-1 was overexpressed in ulcerated tissues and further enhanced by indomethacin, DFU, and SC-560, but not by celecoxib or valdecoxib. PCNA expression in ulcerated areas was reduced by indomethacin, but not by the other test drugs. The expression of activated caspase-3 in ulcers was increased and enhanced further by indomethacin, DFU, and SC-560, but not by celecoxib and valdecoxib. These findings indicate that: 1) COX inhibitors exert differential impairing effects on gastric ulcer healing, through mechanisms unrelated to the inhibition of COX isoforms and prostaglandin production; and 2) NAG-1 induction, followed by activation of proapoptotic pathways, can contribute to the impairing effects of COX inhibitors on ulcer healing.

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Section: Nsaid-activated Gene and Gastric Ulcer Healing 147supporting

confidence: 55%

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Plays a Role in the Impairing Effects of Cyclooxygenase Inhibitors on Gastric Ulcer Healing

Colucci¹,

Antonioli²,

Bernardini³

et al. 2012

J Pharmacol Exp Ther

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“…Yamaguchi et al cloned the canine NAG-1 gene and investigated its expression in canine tissues [17]. The predicted canine NAG-1 amino acid sequence revealed nine cysteine residues and an RXXR sequence that was conserved in the human, mouse, and rat, suggesting that canine NAG-1 protein may have similar biological activity to other species.…”

Section: Biochemistry Of Nag-1mentioning

confidence: 99%

“…The predicted canine NAG-1 amino acid sequence revealed nine cysteine residues and an RXXR sequence that was conserved in the human, mouse, and rat, suggesting that canine NAG-1 protein may have similar biological activity to other species. The canine NAG-1 is induced by several NSAIDs, with the most robust up-regulation by piroxicam in osteosarcoma cells [17]. The secreted and pro-forms of NAG-1 were detected in canine tissues by western blot analysis.…”

Section: Biochemistry Of Nag-1mentioning

confidence: 99%

The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer

Wang

Baek

Eling

2013

Biochemical Pharmacology

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133

155

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Nonsteroidal anti-inflammatory drug (NSAID) activated gene-1, NAG-1, is a divergent member of the transforming growth factor-beta (TGF-β) superfamily that plays a complex but poorly understood role in several human diseases including cancer. NAG-1 expression is substantially increased during cancer development and progression especially in gastrointestinal, prostate, pancreatic, colorectal, breast, melanoma, and glioblastoma brain tumors. Aberrant increases in the serum levels of secreted NAG-1 correlate with poor prognosis and patient survival rates in some cancers. In contrast, the expression of NAG-1 is up-regulated by several tumor suppressor pathways including p53, GSK-3β, and EGR-1. NAG-1 expression is also induced by many drugs and dietary compounds which are documented to prevent the development and progression of cancer in mouse models. Studies with transgenic mice expressing human NAG-1 demonstrated that the expression of NAG-1 inhibits the development of intestinal tumors and prostate tumors in animal models. Laboratory and clinical evidence suggest that NAG-1, like other TGF-β family members, may have different or pleiotropic functions in the early and late stages of carcinogenesis. Upon understanding the molecular mechanism and function of NAG-1 during carcinogenesis, NAG-1 may serve as a potential biomarker for the diagnosis and prognosis of cancer and a therapeutic target for the inhibition and treatment of cancer development and progression.

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“…We recently cloned the canine NAG-1 gene and investigated its expression in canine tissues. 119 The predicted canine NAG-1 amino acid sequence has 9 cysteine residues and an RXXR sequence also conserved with human, mouse, rat, and chimpanzee NAG-1, suggesting that canine NAG-1 protein may have a similar biologic activity to other species. In fact, canine NAG-1 is induced by several NSAIDs, with the most robust upregulation by piroxicam in osteosarcoma cells.…”

Section: Nsaid-activated Gene-1 (Nag-1)mentioning

confidence: 93%

Review Paper: Cancer Chemopreventive Compounds and Canine Cancer

2009

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Abstract. Canine cancer has become more prevalent in recent years because of increased life expectancy and greater attention to the health of pets. The range of cancers seen in dogs is as diverse as that in human patients, and despite more intensive therapeutic interventions, fatality rates remain unacceptably high in both species. Chemoprevention is therefore an important means of confronting this disease. Because domestic pets share our environment, greater cross-application and study of the protumorigenic and antitumorigenic factors in our shared environment will benefit all species, leading to the development of new families of less toxic antitumorigenic compounds based on novel and established molecular targets. Currently, the most interesting cancer preventive agents are nonsteroidal antiinflammatory drugs, peroxisome proliferator-activated receptor-c ligands, and dietary compounds. This article provides an overview of what is known about how these agents affect molecular signaling in neoplastic disease, with reference to reported application and/or study in dogs where available.

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Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1)

Cited by 10 publications

References 32 publications

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Plays a Role in the Impairing Effects of Cyclooxygenase Inhibitors on Gastric Ulcer Healing

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Plays a Role in the Impairing Effects of Cyclooxygenase Inhibitors on Gastric Ulcer Healing

The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer

Review Paper: Cancer Chemopreventive Compounds and Canine Cancer

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