Examination of the role of endopeptidase 3.4.24.15 in A beta secretion by human transfected cells

British Journal of Pharmacology
N ChevallierFrédéric Checler

Abstract

1. We have taken advantage of our recent development of highly potent and specific phosphinic inhibitors of endopeptidase 3.4.24.15 to examine the putative contribution of the enzyme in the secretion of A beta by HK293 transfected cells overexpressing the wild type and the Swedish (Sw) double mutated form of beta APP751. 2. First, we showed that HK293 cells contain a peptidase activity, the inhibition profile of which fully matches that of purified endopeptidase 3.4.24.15. Second, we established that the treatment of HK293 cells with specific phosphinic inhibitors leads to about 80% inhibition of intracellular endopeptidase 3.4.24.15 activity, indicating that these inhibitors penetrate the cells. 3. Metabolic labelling of wild type and Sw beta APP751-expressing cells, followed by immunoprecipitation of A beta-containing peptides, revealed the secretion of A beta and the intracellular formation of an A beta-containing 12 kDa product. 4. A beta secretion by Sw beta APP751 transfected cells was drastically enhanced when compared to cells expressing wild type beta APP751. This production was not affected by endopeptidase 3.4.24.15 inhibitors in either cell type. This correlates well with the observation that endopeptidase 3.4.24.15...Continue Reading

References

Jan 1, 1992·Life Sciences·G Bissette, B Myers
Sep 1, 1992·Trends in Neurosciences·S M Gentleman
Jan 1, 1992·Acta Neurologica Scandinavica. Supplementum·A Nordberg
Jan 1, 1992·Alzheimer Disease and Associated Disorders·C L Joachim, D J Selkoe
Jun 15, 1992·Biochemical and Biophysical Research Communications·J R McDermottA M Gibson
Apr 1, 1991·Neuron·D J Selkoe
Oct 1, 1991·Trends in Pharmacological Sciences·J Hardy, D Allsop
Apr 1, 1990·Analytical Biochemistry·U TisljarA J Barrett
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
Jan 26, 1988·Biochemistry·M OrlowskiC J Molineaux
Jan 1, 1986·British Medical Bulletin·E K Perry
Apr 6, 1984·European Journal of Pharmacology·L VécseiG Telegdy
Oct 1, 1993·Trends in Neurosciences·M Mullan, F Crawford
Nov 1, 1993·Trends in Neurosciences·M Goedert
Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·G D Schellenberg
Apr 26, 1995·Biochemical and Biophysical Research Communications·R A LewA I Smith
Mar 7, 1997·Brain Research·N ChevallierF Checler

❮ Previous
Next ❯

Citations

Dec 21, 2011·The Journal of Biological Chemistry·Marie-Victoire Guillot-SestierFrédéric Checler
Mar 9, 2005·British Journal of Pharmacology·Solveig Lefranc-JullienFrédéric Checler
Feb 4, 2009·Journal of Neurochemistry·Jean SevalleFrédéric Checler
Oct 10, 2002·Endocrine Reviews·Corie N ShrimptonRebecca A Lew
Feb 12, 2008·The Journal of Biological Chemistry·Virginie Buggia-PrevotFrédéric Checler
Jun 22, 1999·The Journal of Biological Chemistry·R YaminC R Abraham
Apr 20, 1999·Biochemical and Biophysical Research Communications·H BarelliF Checler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.