Glutamate carboxypeptidase II is not an amyloid peptide‐degrading enzyme. Issue 7 (23rd March 2013)
- Record Type:
- Journal Article
- Title:
- Glutamate carboxypeptidase II is not an amyloid peptide‐degrading enzyme. Issue 7 (23rd March 2013)
- Main Title:
- Glutamate carboxypeptidase II is not an amyloid peptide‐degrading enzyme
- Authors:
- Alt, Jesse
Stathis, Marigo
Rojas, Camilo
Slusher, Barbara - Abstract:
- Abstract : Glutamate carboxypeptidase II (GCPII) is an exopeptidase that catalyzes the hydrolysis of N ‐acetylated aspartate‐glutamate (NAAG) to N ‐acetyl aspartate (NAA) and glutamate. Consequently, GCPII inhibition has been of interest for the treatment of central and peripheral nervous system diseases associated with excess glutamate. Recently, it was reported that GCPII can also serve as an endopeptidase cleaving amyloid β (Aβ) peptides and that its inhibition could increase the risk of Alzheimer's disease by increasing brain Aβ levels. This study aimed to corroborate and extend these new findings. We incubated Aβ peptides (20 μM) with human recombinant GCPII (300 ng/ml) and monitored the appearance of degradation products by mass spectrometry. Aβ peptides remained intact after 18 h incubation with GCPII. Under the same experimental conditions, Aβ1–40 (20 μM) was incubated with neprilysin (300 ng/ml), an endopeptidase known to hydrolyze Aβ1–40 and the expected cleavage products were observed. GCPII was confirmed active by catalyzing the complete hydrolysis of NAAG (100 μM). We also studied the hydrolysis of [ 3 H]‐NAAG (30 nM) catalyzed by GCPII (40 pM) in the presence of Aβ peptides (picomolar to micromolar range). The addition of Aβ peptides did not alter [ 3 H]‐NAAG hydrolysis. We conclude that GCPII is not an amyloid peptide‐degrading enzyme.—Alt, J., Stathis, M., Rojas, C., Slusher. Glutamate carboxypeptidase II is not an amyloid peptide‐degrading enzyme. FASEB J.Abstract : Glutamate carboxypeptidase II (GCPII) is an exopeptidase that catalyzes the hydrolysis of N ‐acetylated aspartate‐glutamate (NAAG) to N ‐acetyl aspartate (NAA) and glutamate. Consequently, GCPII inhibition has been of interest for the treatment of central and peripheral nervous system diseases associated with excess glutamate. Recently, it was reported that GCPII can also serve as an endopeptidase cleaving amyloid β (Aβ) peptides and that its inhibition could increase the risk of Alzheimer's disease by increasing brain Aβ levels. This study aimed to corroborate and extend these new findings. We incubated Aβ peptides (20 μM) with human recombinant GCPII (300 ng/ml) and monitored the appearance of degradation products by mass spectrometry. Aβ peptides remained intact after 18 h incubation with GCPII. Under the same experimental conditions, Aβ1–40 (20 μM) was incubated with neprilysin (300 ng/ml), an endopeptidase known to hydrolyze Aβ1–40 and the expected cleavage products were observed. GCPII was confirmed active by catalyzing the complete hydrolysis of NAAG (100 μM). We also studied the hydrolysis of [ 3 H]‐NAAG (30 nM) catalyzed by GCPII (40 pM) in the presence of Aβ peptides (picomolar to micromolar range). The addition of Aβ peptides did not alter [ 3 H]‐NAAG hydrolysis. We conclude that GCPII is not an amyloid peptide‐degrading enzyme.—Alt, J., Stathis, M., Rojas, C., Slusher. Glutamate carboxypeptidase II is not an amyloid peptide‐degrading enzyme. FASEB J. 27, 2620‐2625 (2013). www.fasebj.org … (more)
- Is Part Of:
- FASEB journal. Volume 27:Issue 7(2013)
- Journal:
- FASEB journal
- Issue:
- Volume 27:Issue 7(2013)
- Issue Display:
- Volume 27, Issue 7 (2013)
- Year:
- 2013
- Volume:
- 27
- Issue:
- 7
- Issue Sort Value:
- 2013-0027-0007-0000
- Page Start:
- 2620
- Page End:
- 2625
- Publication Date:
- 2013-03-23
- Subjects:
- Alzheimer's disease -- prostate‐specific membrane antigen
Biology -- Periodicals
Biology, Experimental -- Periodicals
570 - Journal URLs:
- http://onlinelibrary.wiley.com/ ↗
- DOI:
- 10.1096/fj.12-225102 ↗
- Languages:
- English
- ISSNs:
- 0892-6638
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - BLDSS-3PM
British Library HMNTS - ELD Digital store - Ingest File:
- 13221.xml