Aminopeptidase N mediates the utilization of the GSH precursor CysGly by cultured neurons
Abstract
Neurons in culture rely on the supply of exogenous cysteine for their glutathione synthesis. After application of cysteine to neuron‐rich primary cultures, the glutathione content was doubled after a 4‐hr incubation. The dipeptide cysteinylglycine (CysGly) was able to substitute for cysteine as exogenous glutathione precursor. In kidneys, the ectopeptidase aminopeptidase N (ApN) has been reported to hydrolyze CysGly. Expression of mRNA of ApN in rat brain and cultured rat neurons was demonstrated by reverse transcriptase polymerase chain reaction and sequencing of the cDNA fragment obtained. In addition, the presence of ApN protein in cultured neurons was demonstrated by its immunocytochemical localization. In the presence of an activity‐inhibiting antiserum against ApN the utilization of CysGly as neuronal glutathione precursor was completely prevented, whereas that of cysteine plus glycine was not affected. The data presented demonstrates that cultured rat neurons express ApN and that this ectopeptidase participates in the utilization of CysGly as precursor for neuronal glutathione. © 2001 Wiley‐Liss, Inc.
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CysGly appears not to be directly taken up by neurons but is rather hydrolyzed extracellularly before the liberated amino acids cysteine and glycine are taken up into neurons.
“CysGly appears not to be directly taken up by neurons but is rather hydrolyzed extracellularly before the liberated amino acids cysteine and glycine are taken up into neurons (Figure 1).”
From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Dringen et al. 2001
Neuronal aminopeptidase N is responsible for the hydrolysis of CysGly, as demonstrated by the ability of an inactivating specific antibody against aminopeptidase N to prevent the utilization of CysGly for neuronal GSH synthesis.
“Responsible for the hydrolysis of CysGly is the neuronal aminopeptidase N, as demonstrated by the ability of an inactivating specific antibody against aminopeptidase N to prevent the utilization of CysGly for neuronal GSH synthesis (Dringen et al. 2001).”
From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Dringen et al. 2001
Both the chemical reduction of extracellular cystine by GSH released from astrocytes and transfer via extracellular vesicles should not be affected by inhibitors of the astrocytic γGT or neuronal aminopeptidase N.
“However, both the chemical reduction of extracellular cystine by GSH released from astrocytes as well as transfer via extracellular vesicles should not be affected by inhibitors of the astrocytic γGT or neuronal aminopeptidase N, which were shown to be involved in the supply of cysteine to neurons (Dringen, Pfeiffer, et al. 1999) and in the use of CysGly by neurons (Dringen et al. 2001).”
From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Dringen et al. 2001
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Self-citation
- Authors
- Dringen, R., Gutterer, J. M., Gros, C., & Hirrlinger, J.
- Affiliations
- University of Tübingen (DE)
- Inserm (FR)
- Corresponding author
- Dringen, Ralf
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2001-11-30
- Volume
- 66
- Issue
- 5
- Pages
- 1003-1008
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W1977642609
- Cited by
- 104
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 6 · 2013: 6 · 2012: 9
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Keywords
- CD13, cysteinylglycine, glutathione synthesis, cysteine, glutathione precursor, cultured neurons, cysteine metabolism, brain
- MeSH terms
- Animals, Cells, Cultured, Central Nervous System, Cysteine, Dipeptides, Fetus, Glutathione, Glycine, Immunohistochemistry, Neurons, RNA, Messenger, Rats, Wistar, Reactive Oxygen Species, DNA, Complementary, Oxidative Stress, CD13 Antigens, Neurodegenerative Diseases, Reverse Transcriptase Polymerase Chain Reaction, Rats
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