NDLI: In Vitro Studies on Degradation of Gamma-L-Glutamyl-L-Cysteine and Gamma-L-Glutamyl-D-Cysteine in Blood: Implications for Treatment of Stroke.

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In Vitro Studies on Degradation of Gamma-L-Glutamyl-L-Cysteine and Gamma-L-Glutamyl-D-Cysteine in Blood: Implications for Treatment of Stroke.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ikpa, Nsisong Forman, Rachel Garchow, Kendra Sukowski, Ernest Peterson, Darryl R.
Description	Country affiliation: Israel Author Affiliation: Ikpa N ( Departments of 1Physiology and Biophysics and 2Medicine, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL.)
Abstract	Treatment for ischemic stroke involves a thrombolytic agent to re-establish blood flow in the brain. However, delayed reperfusion may cause injury to brain capillaries. Previous studies indicate that the antioxidant gamma-L-glutamyl-L-cysteine (Î³-Glu-Cys) contributes to reducing reperfusion injury to the cerebral vasculature in rats, when administered intravascularly. To determine the stability of Î³-Glu-Cys in blood, the peptide was incubated in rat serum in vitro, and its degradation was quantified by high-pressure liquid chromatography. The half-time (t1/2) for degradation of Î³-Glu-Cys was 11 ± 1 minute (mean ± SD, n = 3). A similar pattern of degradation was observed when Î³-Glu-Cys was incubated in the presence of human plasma (t1/2 = 17 ± 8 minutes, n = 3). In a second series of experiments, degradation of an analog (Î³-Glu-D-Cys) was tested in rat serum and found to be more stable than the native molecule. The initial velocity for degradation of Î³-Glu-D-Cys (0.12 ± 0.02 mM/min; mean ± SD, n = 3) was significantly (P = 0.006) less than that of Î³-Glu-Cys (0.22 ± 0.03 mM/min; mean ± SD, n = 3). Furthermore, an in vitro assay indicated that the analog has as an oxidative capacity that equals that of the original peptide in the presence of rat serum and human plasma. Finally, both peptides were found to be similarly effective in preventing lysis of intact cells using in vitro assays. These studies show that Î³-Glu-Cys remains intact in blood for several minutes, and the analog Î³-Glu-D-Cys may be a more stable, but similarly effective antioxidant.
File Format	HTM / HTML
ISSN	10752765
Issue Number	4
Volume Number	22
e-ISSN	15363686
Journal	American Journal of Therapeutics
Language	English
Publisher	Lippincott Williams & Wilkins
Publisher Date	2015-07-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Antioxidants Therapeutic Use Dipeptides Blood Metabolism Fibrinolytic Agents Glutathione Transferase Glutathione Stroke Drug Therapy Animals Humans Models, Animal Protein Stability Proteolysis Rats Time Factors Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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