Expression of Nicotinamide N-Methyltransferase (E.C. 2.1.1.1) in the Parkinsonian Brain

Parsons, Richard B.; Smith, Marie-Louise; Williams, Adrian; Waring, R. H.; Ramsden, D.

doi:10.1093/jnen/61.2.111

Cited by 80 publications

(108 citation statements)

References 38 publications

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“…Urinary excretion of MNA is increased and excretion of pyridone, its catabolic product, is reduced in PD patients [16] . PD patients show higher levels of NNMT activity and protein in brain tissue than controls [17] . MNA destroys several subunits of cerebral complex I, particularly 30-kDa protein [18] , and MNA injection into the rat substantia nigra pars compacta significantly decreases the dopamine content in the striatum [19] .…”

Section: Introductionmentioning

confidence: 83%

Relationship between Blood Levels of Heavy Metals and Parkinson’s Disease in China

Fukushima¹,

Tan²,

Luo³

et al. 2009

Neuroepidemiology

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Background: Idiopathic Parkinson’s disease (PD) and the Parkinsonian syndrome caused by manganese (Mn) poisoning are known to be indistinguishable in terms of symptoms. We thus suspect that many patients who have accumulated Mn in the body in daily life are diagnosed as having idiopathic PD. We examined the relationship between PD and blood levels of heavy metals, and the influence of intake from food in a general population. Methods: The subjects comprised PD patients and sex- and age-matched controls recruited from the outpatient clinic of Xiangfan No. 1 People’s Hospital in Hubei, China, between 2006 and 2008. Information was obtained on previous eating habits before diagnosis of PD and other factors. Morning blood samples were collected before breakfast and were used to measure concentrations of metals. Results: The whole-blood Mn and serum iron (Fe) levels were significantly higher in PD patients than in controls. However, no differences in intake of each metal from food or experience of Mn poisoning were seen between the groups. Conclusions: In China, accumulation of Mn and Fe via unknown routes might be involved in the etiology of PD in the general population.

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Section: Introductionmentioning

confidence: 83%

Relationship between Blood Levels of Heavy Metals and Parkinson’s Disease in China

Fukushima¹,

Tan²,

Luo³

et al. 2009

Neuroepidemiology

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“…NNMT was first identified by cDNA cloning from the liver and the protein is predicted to be present in the cytosol (Aksoy et al, 1995). Several diseases are associated with abnormal nicotinamide metabolism resulting in the production of elevated levels of N-methylnicotinamide; these include Parkinson's disease and hepatic cirrhosis (Cuomo et al, 1994;Parsons et al, 2002). Recently, NNMT was reported as novel serum markers of human colorectal cancer as potential candidates for noninvasive detection of early colorectal neoplasm (Roessler et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of nicotinamide N-methyltransferase in gastric cancer tissues and its potential post-translational modification

Lim

Cho²,

Kim³

et al. 2006

Exp Mol Med

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Gastric cancer is one of the most common cancers worldwide. The purpose of this study was to find out potential markers for gastric cancer. Tumor and normal tissues from 152 gastric cancer cases were analyzed by two-dimensional gel electrophoresis (2-DE). The images of silver stained gels were analyzed and statistical analysis of spot intensities revealed that spot 4262 showed higher expression (5.7-fold increase) in cancer tissues than in normal tissues (P ＜0.001). It was identified by peptide mass fingerprinting as nicotinamide N-methyltransferase (NNMT). A monoclonal antibody with a detection limit down to 10 ng was produced against NNMT in mouse. Using the prepared monoclonal antibody, western blot analysis of NNMT was performed for gastric tissues from 15 gastric cancer patients and two gastric ulcer patients. The results corroborated those of 2-DE experiments. A single spot was detected in gastric ulcer tissues while four to five spots were detected in gastric cancer tissues. In cancer tissues, two additional spots of acidic and basic form were mainly detected on 2-DE gels. This suggests that NNMT receives a post-translational modification in cancer-specific manner.

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“…First, there was an abundance of available post mortem tissue from PD cases, compared to regions more substantially affected by PD, such as the substantia nigra. Second, dopaminergic neuronal transmission occurs in the cerebellum, including dopaminergic input from the substantia nigra, while remaining largely unaffected by PD pathology and neuronal degeneration (Hurley et al, 2003;Parsons et al, 2002). We also genotyped the aforementioned SNPs using DNA extracted from the brain tissue and assessed whether any SNP had an effect on the expression of SPR.…”

Section: Introductionmentioning

confidence: 99%

Sepiapterin reductase expression is increased in Parkinson's disease brain tissue

et al. 2007

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The PARK3 locus on chromosome 2p13 has shown linkage to both the development and age of onset of Parkinson's disease (PD). One candidate gene at this locus is sepiapterin reductase (SPR). Sepiapterin reductase catalyzes the final step in the biosynthetic pathway of tetrahydrobiopterin (BH 4 ), an essential cofactor for aromatic amino acid hydrolases including tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. The expression of SPR was assayed using semiquantitative real-time RT-PCR in human post-mortem cerebellar tissue from neuropathologically confirmed PD cases and neurologically normal controls. The expression of other enzymes involved in BH 4 biosynthesis, including aldose reductase (AKR1B1), carbonyl reductase (CBR1 and CBR3), GTP-cyclohydrolase I (GCH1), and 6-pyruvoyltetrahydrobiopterin (PTS), was also examined. Single-nucleotide polymorphisms around the SPR gene that have been previously reported to show association to PD affection and onset age were genotyped in these samples. Expression of SPR showed a significant 4-fold increase in PD cases relative to controls, while the expression of AKR1B1 and PTS was significantly decreased in PD cases. No difference in expression was detected for CBR1, CBR3, and GCH1. Genetic variants did not show a significant effect on SPR expression, however, this is likely due to the low frequency of rare genotypes in the sample. While the association of SPR to PD is not strong enough to support that this is the PARK3 gene, this study further implicates a role for SPR in idiopathic PD.

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Expression of Nicotinamide N-Methyltransferase (E.C. 2.1.1.1) in the Parkinsonian Brain

Cited by 80 publications

References 38 publications

Relationship between Blood Levels of Heavy Metals and Parkinson’s Disease in China

Relationship between Blood Levels of Heavy Metals and Parkinson’s Disease in China

Overexpression of nicotinamide N-methyltransferase in gastric cancer tissues and its potential post-translational modification

Sepiapterin reductase expression is increased in Parkinson's disease brain tissue

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