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Mackinnon JC, Huether P, Kalisch BE. Effects of nerve growth factor and nitric oxide synthase inhibitors on amyloid precursor protein mRNA levels and protein stability. Open Biochem J. 2012;6:31-9doi: 10.2174/1874091X01206010031.
Mackinnon, J. C., Huether, P., & Kalisch, B. E. (2012). Effects of nerve growth factor and nitric oxide synthase inhibitors on amyloid precursor protein mRNA levels and protein stability. The open biochemistry journal, 631-9. https://doi.org/10.2174/1874091X01206010031
Mackinnon, Janet C, et al. "Effects of nerve growth factor and nitric oxide synthase inhibitors on amyloid precursor protein mRNA levels and protein stability." The open biochemistry journal vol. 6 (2012): 31-9. doi: https://doi.org/10.2174/1874091X01206010031
Mackinnon JC, Huether P, Kalisch BE. Effects of nerve growth factor and nitric oxide synthase inhibitors on amyloid precursor protein mRNA levels and protein stability. Open Biochem J. 2012;6:31-9. doi: 10.2174/1874091X01206010031. Epub 2012 Apr 19. PMID: 22550546; PMCID: PMC3339428.
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Open Biochem J. 2012;6:31-9. doi: 10.2174/1874091X01206010031. Epub 2012 Apr 19.

Effects of nerve growth factor and nitric oxide synthase inhibitors on amyloid precursor protein mRNA levels and protein stability.

The open biochemistry journal

Janet C Mackinnon, Patricia Huether, Bettina E Kalisch

Affiliations

  1. Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.

PMID: 22550546 PMCID: PMC3339428 DOI: 10.2174/1874091X01206010031

Abstract

We determined previously that nitric oxide (NO) modulates the nerve growth factor (NGF)-mediated increases in amyloid precursor protein (APP) levels in PC12 cells. To elucidate potential mechanisms, the effects of NGF and NO synthase (NOS) inhibitors on APP mRNA levels and protein stability were evaluated. Surprisingly, treatment of PC12 cells with NGF resulted in decreased levels of APP695 and APP751/770 mRNA. Therefore, the effect of NGF on APP protein stability was examined using the translation inhibitor, cycloheximide. Under these conditions, NGF did not alter the rate of APP degradation, suggesting that NGF may be enhancing the translation rate of APP. Since NOS inhibitors attenuate the NGF-mediated increase in APP levels, their effect on APP mRNA levels and protein stability was also assessed. S-methylisothiourea (S-MIU), selective for inducible NOS, decreased both APP695 and APP751/770 mRNA levels while the non-selective NOS inhibitor, N(ω)-nitro-L-arginine methylester (L-NAME) had no effect. In both control and NGF-treated PC12 cells, S-MIU increased the half-life of APP, with the greatest effect observed with the APP695 isoform. Based on these data we propose that in PC12 cells, NGF increases APP levels through enhanced translation rate and that NO, which modulates the NGF-induced increase in APP protein, also regulates APP mRNA levels and could play a role in APP processing.

Keywords: Amyloid precursor protein; PC12 cells; mRNA; nerve growth factor; nitric oxide; protein stability.

References

  1. J Neurochem. 1998 Mar;70(3):1009-16 - PubMed
  2. Neuron. 1988 Oct;1(8):669-77 - PubMed
  3. Anal Biochem. 1976 May 7;72:248-54 - PubMed
  4. Brain Res Mol Brain Res. 1993 Apr;18(1-2):127-32 - PubMed
  5. J Neurochem. 1996 Jul;67(1):98-104 - PubMed
  6. J Neurosci. 1999 Jun 1;19(11):4421-7 - PubMed
  7. Nature. 1995 May 4;375(6526):68-73 - PubMed
  8. Ann N Y Acad Sci. 2002 Nov;973:463-7 - PubMed
  9. Neurosci Lett. 2010 Feb 12;470(2):106-10 - PubMed
  10. Br J Pharmacol. 1995 Jan;114(2):510-6 - PubMed
  11. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3032-6 - PubMed
  12. J Neurochem. 2001 Jul;78(1):109-20 - PubMed
  13. Brain Res Mol Brain Res. 1993 Jan;17(1-2):17-22 - PubMed
  14. Annu Rev Neurosci. 1994;17:489-517 - PubMed
  15. J Neurochem. 2007 Apr;101(2):422-33 - PubMed
  16. Biochem Biophys Res Commun. 1989 Dec 29;165(3):1406-14 - PubMed
  17. J Neurochem. 2002 May;81(3):624-35 - PubMed
  18. Brain Res Mol Brain Res. 1997 Dec 1;52(1):71-7 - PubMed
  19. J Neurochem. 2007 Jun;101(5):1172-84 - PubMed
  20. FASEB J. 2001 Jun;15(8):1463-5 - PubMed
  21. J Neurosci Res. 2001 Mar 1;63(5):410-20 - PubMed
  22. Nature. 1988 Feb 11;331(6156):528-30 - PubMed
  23. J Neurochem. 2003 Dec;87(6):1321-32 - PubMed
  24. Cell Mol Life Sci. 2009 Jul;66(14):2299-318 - PubMed
  25. J Biol Chem. 2000 May 26;275(21):15839-44 - PubMed
  26. Neuroreport. 1997 Jul 7;8(9-10):2321-4 - PubMed
  27. Behav Brain Res. 1993 Nov 30;57(2):255-61 - PubMed
  28. Biochem Biophys Res Commun. 1990 Feb 14;166(3):1192-200 - PubMed
  29. J Neurochem. 1998 Aug;71(2):757-66 - PubMed
  30. J Neurochem. 2001 May;77(4):1077-84 - PubMed
  31. Neuron. 1992 Jul;9(1):129-37 - PubMed
  32. Neurochem Res. 2003 Oct;28(10):1553-61 - PubMed
  33. J Biol Chem. 2001 Jul 20;276(29):27272-80 - PubMed

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