The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization
Abstract
Lipoic acid (thiotic acid) is being used as a dietary supplement, and as a therapeutic agent, and is reported to have beneficial effects in disorders associated with oxidative stress, but its mechanism of action remains unclear. We present evidence that lipoic acid induces a substantial increase in cellular reduced glutathione in cultured human Jurkat T cells, human erythrocytes, C6 glial cells, NB41A3 neuroblastoma cells, and peripheral blood lymphocytes. The effect depends on metabolic reduction of lipoic acid to dihydrolipoic acid. Dihydrolipoic acid is released into the culture medium where it reduces cystine. Cysteine thus formed is readily taken up by the neutral amino acid transport system and utilized for glutathione synthesis. By this mechanism lipoic acid enables cystine to bypass the χ‐c transport system, which is weakly expressed in lymphocytes and inhibited by glutamate. Thereby lipoic acid enables the key enzyme of glutathione synthesis, γ‐glutamylcysteine synthetase, which is regulated by uptake‐limited cysteine supply, to work at optimum conditions. Flow cytometric analysis of freshly prepared human peripheral blood lymphocytes, using monobromobimane labeling of cellular thiols, reveals that lipoic acid acts mainly to normalize a subpopulation of cells severely compromised in thiol status rather than to increase thiol content beyond physiological levels. Hence lipoic acid may have clinical relevance in restoration of severely glutathione deficient cells.
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Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0039 · Cited by 2,232
Glutathione and its role in cellular functions
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Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
Shay, K. P., Moreau, R. F., Smith, E. J., Smith, A. R., & Hagen, T. M. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.07.026 · Cited by 976
Molecular aspects of lipoic acid in the prevention of diabetes complications
Packer, L., Kraemer, K., & Rimbach, G. (2001) · Nutrition · doi:10.1016/s0899-9007(01)00658-x · Cited by 556
Self-citationCysteine/cystine redox signaling in cardiovascular disease
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Metadata
- Authors
- Han, D., Handelman, G., Marcocci, L., Sen, C. K., Roy, S., Kobuchi, H., Tritschler, H. J., Flohé, L., & Packer, L.
- Venue
- BioFactors
- Publisher
- Wiley
- Published
- 1997-01
- Volume
- 6
- Issue
- 3
- Pages
- 321-338
- ISSN
- 0951-6433 (ISSN-L)
- 1872-8081
- OpenAlex
- W2092271268
- Cited by
- 334
- References
- 48
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- closed
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