Mark McLaughlin
Applied Neurobiology Group, University of Glasgow Veterinary School, Glasgow (361 1 CQH: UK
Elena Rio
Department of Paychiatry, Alzheimers Disease Research Centre,
University of Dundee Medical School, Ninewells Hospital, Dundee DDI 9SY,
UK
Hazel Leith
Department of Paychiatry, Alzheimers Disease Research Centre,
University of Dundee Medical School, Ninewells Hospital, Dundee DDI 9SY,
UK
Kieran Breen
Department of Paychiatry, Alzheimers Disease Research Centre,
University of Dundee Medical School, Ninewells Hospital, Dundee DDI 9SY,
UK
ABSTRACT
The generation of a secreted N-terminal fragment of the amyloid precursor protein (A PPs) can be stimulated by a variety of signaling pathways many of which are also known to modulate the activity of the phospholipase D (PLD) enzyme. This study used primary rat neuronal cerebellar granule (CG) cultures and SH-SY5Y human neuroblastoma cell lines to determine the potential role of PLD in the protein kinase C (PKC)-associated generation of A PPs. Protein release was markedly enhanced by direct PKC stimulation following treatment of both cell type with either phorbol ester or indirectly by the muscarinic agonist carbachol and these effects were greatly attenuated by co-incubation with the PKC inhibitor GF109203X. A partial inhibition of PKC- and carbachol-stimulated A PPs secretion was also achieved by pre-treatment of the cells with toxin B, a PLD inhibitor. This suggested that PLD may play a role downstream of PKC in the control of A PPs secretion.
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How to cite this article
Mark McLaughlin, Elena Rio, Hazel Leith and Kieran Breen, 2005. The Role of Phospholipase D in Amyloid Precursor Protein Processing. International Journal of Pharmacology, 1: 98-103.
DOI: 10.3923/ijp.2005.98.103
URL: https://scialert.net/abstract/?doi=ijp.2005.98.103
DOI: 10.3923/ijp.2005.98.103
URL: https://scialert.net/abstract/?doi=ijp.2005.98.103
REFERENCES
- Suh, Y.H. and F. Checler, 2002. Amyloid precursor protein, presenilins and alpha-synuclein: Molecular pathogenesis and pharmacological applications in Alzheimer's disease. Pharmacol. Rev., 54: 469-525.
CrossRefDirect Link - Lammich, S., E. Kojro, R. Postina, S. Gilbert and R. Pfeiffer et al., 1999. Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc. Natl. Acad. Sci. USA., 96: 3922-3927.
PubMedDirect Link - Slack, B.E., J. Breu, L. Muchnicki and R.J. Wurtman, 1997. Rapid stimulation of amyloid precursor protein release by epidermal growth factor: Role of protein kinase C. Biochem. J., 327: 245-249.
PubMedDirect Link - Jaffe, A.B., C.D. Toranallerand, P. Greengard and S.E. Gandy, 1994. Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. J. Biol. Chem., 269: 13065-13068.
Direct Link - Budas, G., C.M. Coughlan, J.R. Seckl and K.C. Breen, 1999. The effect of corticosteroids on amyloid β precurosr protein/amyloid precursor-like protein expression and processing in vivo. Neurosci. Lett., 276: 61-64.
CrossRefDirect Link - McLaughlin, M. and K.C. Breen, 1999. Protein kinase C activation potentiates the rapid secretion of the amyloid precursor protein from rat cortical synaptosomes. J. Neurochem., 72: 273-281.
PubMedDirect Link - Wolf, B.A., W.M. Andrew, Y.C. Jolly, Y.P. Robert and W.B. Barry et al., 1995. Muscarinic regulation of Alzheimers-disease amyloid precursor protein secretion and amyloid beta protein production in human neuronal NT2n cells. J. Biol. Chem., 270: 4916-4922.
Direct Link - Kim, S.H., Y.K. Kim, S.J. Jeong, C. Haass, Y.H. Kim and Y.H. Suh, 1997. Enhanced release of secreted form of Alzheimer's amyloid precursor protein from PC12 cells by nicotine. Mol. Pharmacol., 52: 430-436.
Direct Link - Cockcroft, S., 2001. Signalling roles of mammalian phospholipase D1 and D2. Cellular Mol. Life Sci., 58: 1674-1687.
CrossRefDirect Link - Perry, E.K., B.E. Tomlinson, G. Blessed, K. Bergmann, P.H. Gibson and R.H. Perry, 1978. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br. Med. J., 2: 1457-1459.
PubMedDirect Link - DelRio, E., D.G. Nicholls and C.P. Downes, 1994. Involvement of calcium influx in muscarinic cholinergic regulation of phospholipase C in cerebellar granule cells. J. Neurochem., 63: 535-543.
Direct Link - Schmidt, M., U. Rumenapp, C. Bienek, J. Keller, C. Voneichelstreiber and K.H. Jacobs, 1996. Inhibition of receptor signalling to phospholipase D by Clostridium dificle toxin B-role of rho proteins. J. Biol. Chem., 271: 2422-2426.
Direct Link - Del Rio, E., J.A. Bevilacqua, S.J. Marsh, P. Halley and M.P. Caulfield, 1999. Muscarinic M1 receptors activate phosphoinositide turnover and Ca2+ mobilisation in rat sympathetic neurones, but this signalling pathway does not mediate M-current inhibition. J. Physiol. Lond., 520: 101-111.
CrossRefDirect Link - Canet-Aviles, R.M., M. Anderton, N.M. Hooper, A.J. Turner and P.F. Vaughan, 2002. Muscarine enhances soluble amyloid precursor protein secretion in human neuroblastoma SH-SY5Y by a pathway dependent on protein kinase C (alpha), src-tyrosine kinase and extracellular signal-regulated kinase but not phospholipase C. Brain Res. Mol. Brain Res., 102: 62-72.
PubMedDirect Link - Breen, K.C., C.M. Coughlan and F.D. Hayes, 1998. The role of glycoproteins in neural development, function and disease. Mol. Neurobiol., 16: 163-220.
PubMedDirect Link - Buxbaum, J.D., M. Oishi, H.I. Chen, R. Pinkaskramarski, E.A. Jaffe, S.E. Gandy and P. Greengard, 1992. Cholinergic agonists and interleukin-1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein-precursor. Proc. Natl. Acad. Sci. USA., 89: 10075-10078.
PubMedDirect Link - Boyano-Adanez, M.C., C. Lundqvist, C. Larsson and L. Gustavsson, 1997. Characterisation of phospholipase D activation by muscarinic receptors in human neuroblastoma SH-SY5Y cells. Neuropharmacology, 36: 295-304.
CrossRefDirect Link - Humeau, Y., N. Vitale, S. Chasserot-Golaz, J.L. Dupont and G. Du et al., 2001. A role for phospholipase D1 in neurotransmitter release. Proc. Natl. Acad. Sci. USA., 98: 15300-15305.
PubMedDirect Link