Astrocytes Provide Cysteine to Neurons by Releasing Glutathione
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Abstract: Cysteine is the rate‐limiting precursor of glutathione synthesis. Evidence suggests that astrocytes can provide cysteine and/or glutathione to neurons. However, it is still unclear how cysteine is released and what the mechanisms of cysteine maintenance by astrocytes entail. In this report, we analyzed cysteine, glutathione, and related compounds in astrocyte conditioned medium using HPLC methods. In addition to cysteine and glutathione, cysteine‐glutathione disulfide was found in the conditioned medium. In cystine‐free conditioned medium, however, only glutathione was detected. These results suggest that glutathione is released by astrocytes directly and that cysteine is generated from the extracellular thiol/disulfide exchange reaction of cystine and glutathione: glutathione + cystine ↔ cysteine + cysteineglutathione disulfide. Conditioned medium from neuronenriched cultures was also assayed in the same way as astrocyte conditioned medium, and no cysteine or glutathione was detected. This shows that neurons cannot themselves provide thiols but instead rely on astrocytes. We analyzed cysteine and related compounds in rat CSF and in plasma of the carotid artery and internal jugular vein. Our results indicate that cystine is transported from blood to the CNS and that the thiol/disulfide exchange reaction occurs in the brain in vivo. Cysteine and glutathione are unstable and oxidized to their disulfide forms under aerobic conditions. Therefore, constant release of glutathione by astrocytes is essential to maintain stable levels of thiols in the CNS.
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The cysteine supply by astrocytes is initiated by the export of GSH from astrocytes.
“The cysteine supply by astrocytes is initiated by the export of GSH from astrocytes (Dringen, Pfeiffer, et al. 1999; Wang and Cynader 2000)”
From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Wang and Cynader 2000
Exported GSH has been shown to reduce extracellular cystine, thereby liberating cysteine.
“Exported GSH has also been shown to reduce extracellular cystine, thereby liberating cysteine (Wang and Cynader 2000)”
From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Wang and Cynader 2000
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- Authors
- Wang, X. F., & Cynader, M. S.
- Affiliations
- University of British Columbia (CA)
- University of British Columbia Hospital (CA)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2000-04
- Volume
- 74
- Issue
- 4
- Pages
- 1434-1442
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1985451517
- Cited by
- 281
- References
- 1
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 14 · 2020: 15 · 2019: 5 · 2018: 8 · 2017: 3 · 2016: 10 · 2015: 9 · 2014: 11 · 2013: 8 · 2012: 11
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- astrocytes, cysteine, glutathione, cystine, thiol-disulfide exchange, astrocyte-neuron communication, cerebrospinal fluid, glutathione release
- MeSH terms
- Animals, Astrocytes, Carotid Arteries, Cell Communication, Cells, Cultured, Cerebral Cortex, Chromatography, High Pressure Liquid, Cysteine, Female, Glutathione, Jugular Veins, Male, Neurons, Oxidation-Reduction, Pregnancy, Sulfhydryl Compounds, Culture Media, Conditioned, Apoptosis, Oxidative Stress, Glutathione Disulfide, Rats, Long-Evans, Rats
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