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The peptide glycyl-?-histidyl-?-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals.

ABSTRACT: Despite evidence that tripeptide glycyl-?-histidyl-?-lysine (GHK) is an endogenous antioxidant, its mechanism and importance are not fully understood. In the present study, the ability of GHK to reduce levels of reactive oxygen species (ROS) in Caco-2 cells was evaluated by flow cytometry with the oxidation-sensitive fluorescent dye 2',7'-dichlorodihydrofluorescein diacetate. Further, types of ROS diminished by GHK were assessed by utilizing an electron spin resonance (ESR) spin-trapping technique. GHK reduced the tert-butyl hydroperoxide-induced increase in ROS levels in Caco-2 cells at concentrations of 10 µM or less. Experiments utilizing an ESR spin-trapping technique revealed that, among hydroxyl (·OH), superoxide (O2-·), and peroxyl (ROO·) radicals generated by respective chemical reaction systems, GHK diminished signals of both ·OH and ROO·, but not O2-·. Additionally, the GHK effect on the signal of ·OH was much stronger than those of other well-known antioxidative, endogenous peptides, carnosine and reduced glutathione. These results suggest that GHK can function as an endogenous antioxidant in living organisms, possibly by diminishing ·OH and ROO·.

SUBMITTER: Sakuma S

PROVIDER: S-EPMC6055086 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals.

Sakuma Satoru S Ishimura Mai M Yuba Yukinori Y Itoh Yuhki Y Fujimoto Yohko Y

International journal of physiology, pathophysiology and pharmacology 20180625 3

Despite evidence that tripeptide glycyl-ʟ-histidyl-ʟ-lysine (GHK) is an endogenous antioxidant, its mechanism and importance are not fully understood. In the present study, the ability of GHK to reduce levels of reactive oxygen species (ROS) in Caco-2 cells was evaluated by flow cytometry with the oxidation-sensitive fluorescent dye 2',7'-dichlorodihydrofluorescein diacetate. Further, types of ROS diminished by GHK were assessed by utilizing an electron spin resonance (ESR) spin-trapping techniq ...[more]

PMID: 30042814

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Project description:BackgroundSkeletal muscle dysfunction is an important co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD-related skeletal muscle dysfunction. Glycine-histidine-lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti-inflammatory and antioxidant properties. The purpose of this study was to determine whether GHK is involved in COPD-related skeletal muscle dysfunction.MethodsThe plasma GHK level in patients with COPD (n = 9) and age-paired healthy subjects (n = 11) were detected using reversed-phase high-performance liquid chromatography. The complex GHK with Cu (GHK-Cu) was used in in vitro (C2C12 myotubes) and in vivo experiments (cigarette smoking [CS]-exposure mouse model) to explore the involvement of GHK in CS-induced skeletal muscle dysfunction.ResultsCompared with healthy control, plasma GHK levels were decreased in patients with COPD (70.27 ± 38.87 ng/mL vs. 133.0 ± 54.54 ng/mL, P = 0.009). And plasma GHK levels in patients with COPD were associated with pectoralis muscle area (R = 0.684, P = 0.042), inflammatory factor TNF-α (R = -0.696, P = 0.037), and antioxidative stress factor SOD2 (R = 0.721, P = 0.029). GHK-Cu was found to rescue CSE-induced skeletal muscle dysfunction in C2C12 myotubes, as evidenced by increased expression of myosin heavy chain, reduced expression of MuRF1 and atrogin-1, elevated mitochondrial content, and enhanced resistance to oxidative stress. In CS-induced muscle dysfunction C57BL/6 mice, GHK-Cu treatment (0.2 and 2 mg/kg) reduces CS-induced muscle mass loss (skeletal muscle weight (1.19 ± 0.09% vs. 1.29 ± 0.06%, 1.40 ± 0.05%; P < 0.05) and muscle cross-sectional area elevated (1055 ± 552.4 μm2 vs. 1797 ± 620.9 μm2 , 2252 ± 534.0 μm2 ; P < 0.001), and also rescues CS-induced muscle weakness, indicated by improved grip strength (175.5 ± 36.15 g vs. 257.6 ± 37.98 g, 339.1 ± 72.22 g; P < 0.01). Mechanistically, GHK-Cu directly binds and activates SIRT1(the binding energy was -6.1 kcal/mol). Through activating SIRT1 deacetylation, GHK-Cu inhibits FoxO3a transcriptional activity to reduce protein degradation, deacetylates Nrf2 and contribute to its action of reducing oxidative stress by generation of anti-oxidant enzymes, increases PGC-1α expression to promote mitochondrial function. Finally, GHK-Cu could protect mice against CS-induced skeletal muscle dysfunction via SIRT1.ConclusionsPlasma glycyl-l-histidyl-l-lysine level in patients with chronic obstructive pulmonary disease was significantly decreased and was significantly associated with skeletal muscle mass. Exogenous administration of glycyl-l-histidyl-l-lysine-Cu2+ could protect against cigarette smoking-induced skeletal muscle dysfunction via sirtuin 1.

Dataset Information

The peptide glycyl-?-histidyl-?-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals.

Publications

The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals.

Similar Datasets

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