Article ; Online: Glycyl-l-histidyl-l-lysine-Cu
Journal of cachexia, sarcopenia and muscle
2023 Volume 14, Issue 3, Page(s) 1365–1380
Abstract: ... sectional area elevated (1055 ± 552.4 μm: Conclusions: Plasma glycyl-l-histidyl-l-lysine level ... associated with skeletal muscle mass. Exogenous administration of glycyl-l-histidyl-l-lysine-Cu ...
Abstract | Background: Skeletal 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. Methods: The 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. Results: Compared 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 μm Conclusions: Plasma 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-Cu |
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MeSH term(s) | Humans ; Mice ; Animals ; Lysine/metabolism ; Sirtuin 1/metabolism ; Cigarette Smoking ; Mice, Inbred C57BL ; Muscle, Skeletal/metabolism ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Antioxidants/metabolism ; Pulmonary Disease, Chronic Obstructive/metabolism |
Chemical Substances | Lysine (K3Z4F929H6) ; Sirtuin 1 (EC 3.5.1.-) ; Antioxidants |
Language | English |
Publishing date | 2023-03-10 |
Publishing country | Germany |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2586864-0 |
ISSN | 2190-6009 ; 2190-5991 |
ISSN (online) | 2190-6009 |
ISSN | 2190-5991 |
DOI | 10.1002/jcsm.13213 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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