Skip to main content
Log in

The effect of heavy metals on nicotinamideN-methyltransferase activityin vitro relating to Parkinson’s disease

  • Original Article
  • Published:
Environmental Health and Preventive Medicine Aims and scope

Abstract

Objective

The aims of this study were to determine the effects of heavy metals such as manganese on nicotinamideN-methyltransferase (EC 2.1.1.1) (NNMT) activity and to consider the possibility of involvement of NNMT activation in the pathogenesis of heavy metal induced Parkinson’s disease.

Methods

NNMT activity in supernatants separated from brain, liver and kidney homogenates of 5 elderly male Wistar rats by centrifugation were measured by high performance liquid chromatography system with fluorescence. NNMT activity under the conditon of 0.5 or 5.0 mM Mn2+, Fe2+, Cu2+ or Cd2+ was compared with control (no metal ion existence).

Results

NNMT activities in rat brain, liver and kidneys were significantly decreased by Cu2+, and those in the liver and kidneys were significantly decreased by Cd2+. Mn2+ reduced NNMT activity only in the liver. Fe2+ had no effect on NNMT activity.

Conclusions

No metal increased NNMT activity in this study, contrary to our hypothesis. Further study is needed to clarify the reason why the effects of Mn2+ and Fe2+ which have a high relevance to Parkinson’s disease on NNMT activity differ from those of Cu2+ and Cd2+

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Couper J. On the effects of black oxide of manganese when inhaled into the lungs. Br Ann Med Pharm. 1837; 1: 41–42.

    Google Scholar 

  2. Takeda A. Manganese action in brain function. Brain Res Brain Res Rev. 2003; 41: 79–87.

    Article  PubMed  CAS  Google Scholar 

  3. Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, et al. Occupational exposures to metals as risk factors for Parkinson’s disease. Neurology. 1997; 48: 650–658.

    PubMed  CAS  Google Scholar 

  4. Powers KM, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD, et al. Parkinson’s disease risks associated with dietary iron, manganese, and other nutrient intakes. Neurology 2003; 60: 1761–1766.

    PubMed  CAS  Google Scholar 

  5. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidineanalog synthesis. Science. 1983; 219: 979–980.

    Article  PubMed  CAS  Google Scholar 

  6. Gearhart DA, Neafsey EJ, Collins MA. Characterization of brain ß-carboline-2-N-methyltransferase, an enzyme that may play a role in idiopathic Parkinson’s disease. Neurochem Res. 1997; 22: 113–121.

    Article  PubMed  CAS  Google Scholar 

  7. Kotake Y. Tetrahydroisoquinoline derivatives as possible Parkinson’s disease-inducing substances. Yakugaku Zasshi. 2002; 122: 975–982. (Article in Japanese)

    Article  PubMed  CAS  Google Scholar 

  8. Mizuno Y, Sone N, Saitoh T. Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium ion on activities of the enzymes in the electron transport system in mouse brain. J Neurochem. 1987; 48: 1787–1793.

    Article  PubMed  CAS  Google Scholar 

  9. Mizuno Y, Ohta S, Tanaka M, Takamiya S, Suzuki K, Sato T, et al. Deficiencies in complex 1 subunits of the respiratory chain in parkinson’s disease. Biochem Biophys Res Commun. 1989; 163: 1450–1455.

    Article  PubMed  CAS  Google Scholar 

  10. Parker WD Jr, Boyson SJ, Parks JK. Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol. 1989; 26: 719–723.

    Article  PubMed  Google Scholar 

  11. Schapira AH, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, et al. Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem. 1990; 55: 2142–2145.

    Article  PubMed  CAS  Google Scholar 

  12. Williams AC, Pall HS, Steventon GB, Green S, Buttrum S, Molloy H, et al. N-methylation of pyridines and Parkinson’s disease. Adv Neurol. 1993; 60: 194–196.

    PubMed  CAS  Google Scholar 

  13. Parsons RB, Smith ML, Williams AC, Waring RH, Ramsden DB. Expression of nicotinamide N-methyltransferase (E.C. 2.1.1.1) in the Parkinsonian brain. J Neuropathol Exp Neurol. 2002; 61: 111–124.

    PubMed  CAS  Google Scholar 

  14. Fukushima T, Tawara T, Isobe A, Hojo N, Shiwaku K Yamane Y. Radical formation site of cerebral complex I and Parkinson’s disease. J Neurosci Res. 1995; 42: 385–390.

    Article  PubMed  CAS  Google Scholar 

  15. Fukushima T, Kaetsu A, Lim H, Moriyama M. Possible role of I-methylnicotinamide in the pathogenesis of Parkinson’s disease. Exp Toxicol Pathol. 2002; 53: 469–473.

    Article  PubMed  CAS  Google Scholar 

  16. Sano A, Endo N, Takitani S. Fluorometric assay of rat ussue N-methyltransferases with nicotinamide and four isomeric methylnicotinamides. Chem Pharm Bull. 1992; 40: 153–156.

    PubMed  CAS  Google Scholar 

  17. Musfeld C, Biollaz J, Belaz N, Kesselring UW, Decosterd LA. Validation of an HPLC method for the determination of urinary and plasma levels ofN 1-methylnicotinamide, an endogenous marker of renal cationic transport and plasma flow. J Pharm Biomed Anal. 2001; 4: 391–404.

    Article  Google Scholar 

  18. Zhang S, Zhou Z, Fu J. Effect of manganese chloride exposure on liver and brain mitochondria function in rats. Environ Res. 2003; 93: 149–157.

    Article  PubMed  CAS  Google Scholar 

  19. Hanahisa Y, Yamaguchi M. Inhibitory effect of zinc and copper on phosphatase activity in the brain cytosol of rats: involvement of SH groups. Biol Pharm Bull. 1998; 21: 1222–1225.

    PubMed  CAS  Google Scholar 

  20. Fukushima T. Niacin metabolism and Parkinson’s disease. Environ Health Prev Med. 2005; 10: 3–8.

    Article  Google Scholar 

  21. Bandyopadhyay D, Chatterjee AK, Datta AG. Effect of cadmium, mercury and copper on partially purified hepatic flavokinase of rat. Mol Cell Biochem. 1997; 167: 73–80.

    Article  PubMed  CAS  Google Scholar 

  22. Upmeier B, Gross W, Koster S, Barz W. Purification and properties of S-adenosyl-L-methionine:nicotinic acid-N-methyltransferase from cell suspension cultures of Glycine max L. Arch Biochem Biophys. 1988; 262: 445–454.

    Article  PubMed  CAS  Google Scholar 

  23. Aschner M. Manganese: brain transport and emerging research needs. Environ Health Perspect. 2000: 108 Supple 3: 429–432.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tetsuhito Fukushima.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugawara, A., Yokoyama, H., Ohta, M. et al. The effect of heavy metals on nicotinamideN-methyltransferase activityin vitro relating to Parkinson’s disease. Environ Health Prev Med 10, 180–183 (2005). https://doi.org/10.1007/BF02897708

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02897708

Key words

Navigation