Anti-inflammatory effect of 1-methylnicotinamide in contact hypersensitivity to oxazolone in mice; involvement of prostacyclin

Bryniarski, Krzysztof; Biedroń, Rafał; Jakubowski, Andrzej; Chłopicki, Stefan; Marcinkiewicz, Janusz

doi:10.1016/j.ejphar.2007.09.011

Cited by 61 publications

(49 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As already mentioned, NNMT catalyzes the formation ofN'-methylnicotinamide, therefore, NNMT activity may be involved in regulating the biological activity of this endogenous compound. It has recently become apparent that N'-methylnicotinamide possesses anti-inflammatory (14), anti-thrombotic (15), vasoprotective (16), and gastroprotective (17) properties, and its levels were found altered in some diseases including hepatic cirrhosis (18) and atherosclerosis (19). Increased NNMT expression was detected in chronic obstructive pulmonary disease (COPD) (20)(21), and in Parkinson's disease, in which enhanced enzyme activity seems to lead to the production of toxic N-methylpiridinium compounds that have been advanced as possible neurotoxins underlying nigrostriatal degeneration (22).…”

Section: Discussionmentioning

confidence: 99%

Inhibiting Proliferation in KB Cancer Cells by RNA Interference-Mediated Knockdown of Nicotinamide N-Methyltransferase Expression

Pozzi

Mazzotta²,

Muzio

et al. 2011

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

The enzyme Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide and other pyridines, playing a pivotal role in the biotransformation and detoxification of many drugs and xenobiotic compounds. Several tumours have been associated with abnormal NNMT expression, however its role in tumour development remains largely unknown. In this study we investigated expression levels of Nicotinamide N-methyltransferase in a cancer cell line and we evaluated the effect of shRNA-mediated silencing of NNMT on cell proliferation. Cancer cells were examined for NNMT expression by semiquantitative RT-PCR and Western blot analysis. A HPLC-based catalytic assay was performed to assess enzyme activity. Cells were transfected with four shRNA plasmids against NNMT and control cells were treated with transfection reagent only (mock). The efficiency of gene silencing was detected by Real-Time PCR and Western blot analysis. MTT cell proliferation assay and the soft agar colony formation assay were then applied to investigate the functional changes in cancerous cell. NNMT mRNA was detected in cancer cells, showing a very high expression level. In keeping with the results of RT-PCR analysis, the protein level and NNMT enzyme activity were particularly high in KB cells. ShRNA vectors targeted against NNMT efficiently suppressed gene expression, showing inhibition observed at both the mRNA and protein levels. Down-regulation of NNMT significantly inhibited cell proliferation and decreased colony formation ability on soft agar. The present data support the hypothesis that the enzyme plays a role in tumour expansion and its inhibition could represent a possible molecular approach to the treatment of cancer.Tumour arises as a result of gene mutations and abnormal expression that endow the cell with many specific functional capabilities, such as cell proliferation, invasion and metastasis (l). The cellular and biochemical factors that underline cancer dissemination are poorly understood. Treatment of

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibiting Proliferation in KB Cancer Cells by RNA Interference-Mediated Knockdown of Nicotinamide N-Methyltransferase Expression

Pozzi

Mazzotta²,

Muzio

et al. 2011

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

show abstract

“…In addition to IP analogs, "pleiotropic" releasers of endogenous PGI 2 may have cardiovascular protective effects. These drugs include angiotensinconverting enzyme inhibitors, statins, some ␤-adrenergic receptor-blockers, antiplatelet thienopyridines, some antidiabetic drugs such as metformin (Gryglewski, 2008), and N 1 -methyl-nicotinamide (Bryniarski et al, 2008). IP antagonists are being examined as potential analgesics to replace nonselective COX inhibitors, although there remains a concern for the perturbation of the TXA 2 /PGI 2 balance, which could be greater with IP antagonists than with COX2 inhibitors (Jones et al, 2006).…”

Section: G Modulators Of the Prostacyclin Pathway In The Management mentioning

confidence: 99%

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

2012

View full text Add to dashboard Cite

“…Based on the results of this study, we believe that elevated NNMT activity in the liver and other tissues may not be detrimental but that it may promote a compensatory anti-atherosclerotic response. This may be supported by the profile of exogenous MNA's pharmacological activity, including antithrombotic and anti-inflammatory effects mediated by the COX-2/PGI 2 pathway [8,10]. MNA was also shown to reverse endothelial dysfunction and to affect lipid metabolism, but the involvement of the COX-2/PGI 2 pathway was not examined in this regard [5].…”

Section: Discussionmentioning

confidence: 99%

“…NA is a water-soluble vitamin essential for energy supply, cell viability, and resistance to stress or injury [28]. Moreover, it has recently become apparent that MNA, long considered an inactive metabolite of NA, possess anti-thrombotic [10], antiinflammatory [8], gastroprotective [9], and vasoprotective [5] properties.…”

Section: Introductionmentioning

confidence: 99%

Activation of nicotinamide N-methyltrasferase and increased formation of 1-methylnicotinamide (MNA) in atherosclerosis

Mateuszuk

Хомич²,

Słomińska

et al. 2009

Pharmacological Reports

View full text Add to dashboard Cite

Abstract:Nicotinamide N-methyltrasferase (NMMT) catalyzes the conversion of nicotinamide (NA) to 1-methylnicotinamide (MNA). Recent studies have reported that exogenous MNA exerts anti-thrombotic and anti-inflammatory activity, suggesting that endogenous NMMT-derived MNA may play a biological role in the cardiovascular system. In the present study, we assayed changes in hepatic NNMT activity and MNA plasma levels along the progression of atherosclerosis in apoE/LDLR -/-mice, as compared to age-matched wild-type mice. Atherosclerosis progression in apoE/LDLR -/-mice was quantified in aortic root, while hepatic NNMT activity and MNA plasma concentrations were concomitantly measured in 2-, 3-, 4-, and 6-month-old mice. In apoE/LDLR -/-mice, atherosclerotic plaques developed in the aortic roots beginning at the age of 3 months and gradually increased in size, macrophage content, and inflammation intensity over time, as detected by Oil-Red O staining, CD68 immunostaining, and in situ zymography (MMP2/MMP9 activity). Hepatic NNMT activity was upregulated approximately two-fold in apoE/LDLR -/-mice by the age of 2 months, as compared to wild-type mice (1.03 ± 0.14 vs. 0.64 ± 0.23 pmol/min/mg, respectively). MNA plasma concentrations were also elevated approximately two-fold (0.30 ± 0.13 vs. 0.17 ± 0.04 mmol/l, respectively). As atherosclerosis progressed, hepatic NMMT activity and MNA plasma concentrations increased five-fold in 6-month-old apoE/LDLR -/-mice at the stage of advanced atherosclerotic plaques (NMMT activity: 2.29 ± 0.34 pmol/min/mg, MNA concentration: 1.083 ± 0.33 mmol/l). In summary, the present study demonstrated that the progression of vascular inflammation and atherosclerosis was associated with the upregulation of hepatic NNMT activity and subsequent increase in endogenous MNA plasma levels. Given the anti-thrombotic and anti-inflammatory properties of exogenous MNA, robust activation of an endogenous NA-MNA pathway in atherosclerosis may play an important compensatory role.

show abstract

Anti-inflammatory effect of 1-methylnicotinamide in contact hypersensitivity to oxazolone in mice; involvement of prostacyclin

Cited by 61 publications

References 27 publications

Inhibiting Proliferation in KB Cancer Cells by RNA Interference-Mediated Knockdown of Nicotinamide N-Methyltransferase Expression

Inhibiting Proliferation in KB Cancer Cells by RNA Interference-Mediated Knockdown of Nicotinamide N-Methyltransferase Expression

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

Activation of nicotinamide N-methyltrasferase and increased formation of 1-methylnicotinamide (MNA) in atherosclerosis

Contact Info

Product

Resources

About