Hill. D J DJ; Phillips. I D ID; Wang. J F JF; Becks. G P GP
This study looked at how thyroid‑stimulating hormone (TSH) makes thyroid cells in sheep produce more of a protein called basic fibroblast growth factor (FGF). It found that moderate levels of TSH raise the amount of basic FGF mRNA and protein inside the cells and in the surrounding matrix, but very high TSH levels are less effective. The work is purely basic science about thyroid cell biology and does not involve the peptide GHK‑Cu or suggest any practical health protocol.
Wood. A M AM; Bidey. S P SP; Soden. J J; Robertson. W R WR
A lab study on thyroid cells found that both insulin and thyroid‑stimulating hormone (TSH) make the inside of the cells more alkaline (higher pH), with TSH having a stronger effect. This was observed in cultured cells, not in people.
Miller. D M DM; DeSilva. D D; Pickart. L L; Aust. S D SD
The copper binding tripeptide, glycyl-L-histidyl-L-lysine [GHK:Cu(II)] has a plethora of biological effects related to the wound healing process. The presence of iron complexes in damaged tissues is detrimental to wound healing, due to local inflammation, as well as microbial infection mediated by iron. To test if the wound healing properties of GHK:Cu(II) are due to an affect on iron metabolism, we examined the effects of GHK:Cu(II) on iron catalyzed lipid peroxidation. GHK:Cu(II) inhibited lipid peroxidation only if the iron source was ferritin. Whereas GHK:Cu(II) inhibited ferritin iron release it did not exhibit significant superoxide dismutase-like or ceruloplasmin-like activity. We propose that GHK:Cu(II) binds to the channels of ferritin involved in iron release and physically prevents the release of Fe(II). Thus, a biological effect of GHK:Cu(II), possibly related to wound healing, may be the inhibition of ferritin iron release in damaged tissues, preventing inflammation and microbial infections.
Bachrach. L K LK; Liu. F R FR; Burrow. G N GN; Eggo. M C MC
This study looked at how sheep thyroid cells make proteins that bind insulin‑like growth factors (IGFs). It found that under normal lab conditions the cells release several small, non‑glycosylated binding proteins, and that adding growth‑stimulating signals (EGF or phorbol esters) makes the cells produce larger, glycosylated versions. The work is purely basic science and doesn’t give any guidance on using GHK‑Cu or any other peptide for health or performance.
Wang. J F JF; Becks. G P GP; Buckingham. K D KD; Hill. D J DJ
Researchers looked at the proteins that thyroid cells release which can bind insulin‑like growth factors (IGF‑I and IGF‑II). They found several different IGF‑binding proteins of various sizes and showed that hormones in the culture media change how much of each protein is released. The work is basic science and does not give any direct tips for using the GHK‑Cu peptide or for health‑optimizing protocols.
Conato. Chiara C; Kozłowski. Henryk H; Swiatek-Kozłowska. Jolanta J; Młynarz. Piot...
This paper studies how nickel ions stick to a small protein fragment (GHK) and two similar lab-made versions. It’s a pure chemistry investigation and doesn’t tell you anything you can use for health, supplements, or performance.
Ha. Jae Won JW; Choi. Joon Yong JY; Boo. Yong Chool YC
Metal chelators are used for various industrial and medical purposes based on their physicochemical properties and biological activities. In biological systems, copper ions bind to certain enzymes as cofactors to confer catalytic activity or bind to specific proteins for safe storage and transport. However, unbound free copper ions can catalyze the production of reactive oxygen species (ROS), causing oxidative stress and cell death. The present study aims to identify amino acids with copper chelation activities that might mitigate oxidative stress and toxicity in skin cells exposed to copper ions. A total of 20 free amino acids and 20 amidated amino acids were compared for their copper chelation activities in vitro and the cytoprotective effects in cultured HaCaT keratinocytes exposed to CuSO<sub>4</sub>. Among the free amino acids, cysteine showed the highest copper chelation activity, followed by histidine and glutamic acid. Among the amidated amino acids, cysteinamide showed the highest copper chelation activity, followed by histidinamide and aspartic acid. CuSO<sub>4</sub> (0.4-1.0 mM) caused cell death in a concentration-dependent manner. Among the free and amidated amino acids (1.0 mM), only histidine and histidinamide prevented the HaCaT cell death induced by CuSO<sub>4</sub> (1.0 mM). Cysteine and cysteinamide had no cytoprotective effects despite their potent copper-chelating activities. EDTA and GHK-Cu, which were used as reference compounds, had no cytoprotective effects either. Histidine and histidinamide suppressed the CuSO<sub>4</sub>-induced ROS production, glutathione oxidation, lipid peroxidation, and protein carbonylation in HaCaT cells, whereas cysteine and cysteinamide had no such effects. Bovine serum albumin (BSA) showed copper-chelating activity at 0.5-1.0 mM (34-68 mg mL<sup>-1</sup>). Histidine, histidinamide, and BSA at 0.5-1.0 mM enhanced the viability of cells exposed to CuCl<sub>2</sub> or CuSO<sub>4</sub> (0.5 mM or 1.0 mM) whereas cysteine and cysteinamide had no such effects. The results of this study suggest that histidine and histidinamide have more advantageous properties than cysteine and cysteinamide in terms of alleviating copper ion-induced toxic effects in the skin.
Dou. Yan Y; Lee. Amanda A; Zhu. Lida L; Morton. John J; Ladiges. Warren W
GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring peptide found in human serum with levels averaging 200 ng/ml at age 20 but declining to an average of 80 ng/ml by age 60. The molecule has a very high affinity for copper and forms the chelate GHK-Cu. The peptide as well as its Cu (II) chelate have anti-inflammatory and tissue remodeling properties. GHK-Cu has been shown to promote skin remodeling, wound healing and regeneration, and has prominent antioxidant and anti-inflammatory effects in in vitro and in vivo studies. In addition, preliminary observations suggest GHK can partially reverse cognitive impairment in aging mice by targeting anti-inflammatory and epigenetic pathways. The evidence as presented provides the rationale to further investigate this naturally occurring peptide in preclinical and clinical aging studies.
Kukowska. M M; Dzierzbicka. K K
Three decades of extensive research on biological activity of natural tripeptide Gly-His-Lys has established the substructure for development of its novel derivatives which give hope for widening the application in the field of medicine and dermatology. Synthetic approaches to obtain Gly-His-Lys and its modifications provide both classical solution method and solid phase peptide synthesis, usage of different protecting groups and methods of peptide bond formation. In our present review, we emphasize on the methods of the synthesis described in the literature and present the aspects of Gly-His-Lys structure modifications that played a key role in scientific research.
Lok. J B JB; Mika-Grieve. M M; Grieve. R B RB; Chin. T K TK
The study looked at how different lab liquids and supplements affect the growth of heartworm larvae in a dish. It found that common growth media work similarly, fetal calf serum helps the larvae the most, and a commercial supplement works like the serum. The peptide GHK (the focus of interest) did not help the larvae grow at all.
Laussac. J P JP; Pasdeloup. M M; Hadjiliadis. N N
The study looks at how a small blood peptide (glycyl‑histidyl‑lysine) and some nucleotides bind to palladium ions, using NMR spectroscopy to figure out the structures of these complexes. It’s a basic chemistry investigation and doesn’t test any health effects or practical uses.
García-Sáinz. J A JA; Olivares-Reyes. J A JA
Gly-His-Lys, a tripeptide isolated from human plasma that increases the growth rate of many cells, stimulated in dose-dependent fashion the activity of phosphorylase a in isolated rat hepatocytes. Such effect was associated to increases in both IP3 production and [Ca++]i. Interestingly, these effects of Gly-His-Lys were antagonized by losartan, a nonpeptide angiotensin II receptor antagonist (AT1 selective), which suggested that these receptors were involved in its effect. Binding competition experiments using the radioligand [125I][Sar1-Ile8]angiotensin II clearly indicated that Gly-His-Lys interacts with AT1 receptors. It was also observed that other histidine-containing tripeptides were also capable of interacting with these receptors.
Ambesi-Impiombato. F S FS; Parks. L A LA; Coon. H G HG
Primary cultures of rat thyroid cells were made in medium supplemented with 0.1--0.5% calf serum and containing six hormones or growth factors: insulin, thyrotropin, transferrin, hydrocortisone, somatostatin, and glycyl-L-histidyl-L-lysine acetate. The FRTL strain was purified by successive colonial isolations and was found to maintain highly differentiated features (secretion into the culture medium of physiological amounts of thyroglobulin and concentration of iodide by 100-fold). The FRTL strain has been observed for more than 3 years in continuous culture. It has maintained the same biochemical and morphological characteristics that typified the primary cultures of thyroid follicular cells immediately after their enzymatic release from the rat thyroid. Thyroid epithelial cells that were grown under more conventional cell culture conditions failed to retain these specialized characteristics. We show that maintenance in vitro of these specialized functions of rat thyroid follicular cells is dependent on low serum concentrations and supplementation with hormones in the primary cultures. Our observations indicate that this culture strategem may be aplicable to the general problem of maintenance of differentiated characteristics in cultures of other epithelial cells.
Bobyntsev. I I II; Chernysheva. O I OI; Dolgintsev. M E ME; Smakhtin. M Iu MIu; Belykh. A E AE
The intraperitoneal administration of Gly-His-Lys tripeptide to male BALB/c mice 12 min before the beginning of the study at doses 0.5, 1.5, 5, 15, and 50 mg/kg produced analgesic effect in the hot-plate test, which was manifested by an increase in the duration of the latent period of the paw-licking reaction. The replacement of L-lysine by D-lysine in the tripeptide molecule was accompanied by significant weakening of the analgesic effect after administration in the same doses. The attachment of D-alanine to N- or C-end of Gly-His-Lys peptide led to leveling of the analgesic effect. On the contrary, after the administration of these analogs, the duration of the latent period of the paw-licking reaction was increased in almost all experimental groups of animals and reached in some cases significant differences that were indicative of the manifestation of algic effects of the modified peptides.
Pickart. L L; Thaler. M M MM; Millard. M M
Isolation and purification of growth-modulating peptides from biological sources is often accompanied by excessive losses of bioactive material. During the isolation of a growth-modulating tripeptide glycylhistidyllysine (GHL) from human plasma, copper and iron were found to co-isolate with the peptide. Studies with [3H]GHL demonstrated that these metals interfere at several steps of the procedure for the isolation of GHL from plasma (gel filtration chromatography, high-pressure silica-gel). Removal of these metals with an insoluble chelating resin (Cellex 100) enhanced recovery of [3H]GHL from plasma 8-fold. These results suggest that removal of transition metals may aid in the recovery of peptides which are difficult to isolate from biological sources.
Yang. Xinlei X; Zhang. Yu Y; Huang. Cheng C; Lu. Lei L; Chen. Junying J; Weng. Yajun Y
Wound healing in diabetes is retarded by the dysfunctional local microenvironment. Although there are many studies using hydrogels as substitutes for natural extracellular matrices (ECMs), hydrogels that can mimic both the structure and functions of natural ECM remain a challenge. Self-assembling peptide RADA16 nanofiber has distinct advantages to provide a biomimetic extracellular matrix nanofiber structure. However, it still lacks biological cues to promote angiogenesis that is of vital significance for diabetic wound healing. With a customized copper peptide glycyl-histidyl-lysine (GHK) functionalized RADA16, an integrated approach using functionalized RADA16 nanofiber to chelate copper ion, is innovatively proposed in this present study. The acquired composite hydrogel holds the biomimetic nanofiber architecture, and exhibits promoting angiogenesis by both enhancing adhesion and proliferation of endothelial cells (EC) in vitro and neovascularization in vivo. It shows that the functionalized nanofiber scaffolds significantly accelerated wound closure, collagen deposition, and tissue remodeling both in healthy and diabetic mice. Furthermore, immunohistochemical analysis give evidence that an upregulated expression of eNOS and CD31 in the copper peptide-functionalized RADA16 treated group. It can be envisioned that this scaffold can serve as a promising dressing for diabetic wound healing.
Barra. R R
Glycyl-histidyl-lysine (GHL) has been shown to have growth stimulatory effects on a number of different cell types including hepatocytes and hepatoma cells. In this study, the effects of GHL on Morris hepatoma 7777 cells were investigated. The greatest stimulatory effects on 3H-thymidine and 3H-leucine incorporation were observed at a GHL concentration of 2 ng/ml. In randomly proliferating cells, the incorporation of 3H-thymidine into DNA increased by 50% and that of 3H-leucine into protein by 29%. In addition, synergistic effects were observed when insulin and glucagon were included with GHL in the incubation mixture. Experiments with cells rendered quiescent by serum starvation indicated that cells in the G1 phase of the cell cycle are more sensitive to GHL stimulation. In these experiments, 3H-thymidine incorporation increased earlier and peaked at a higher value than in the control cells. This finding suggests that GHL may play a role in stimulating quiescent cells to re-enter the cell cycle.
Zhang. Qin Q; Yan. Liming L; Lu. Jingwen J; Zhou. Xiaoming X
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Min. Jin-Hong JH; Sarlus. Heela H; Harris. Robert A RA
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Conato. C C; Gavioli. R R; Guerrini. R R; Kozlowski. H H; Mlynarz. P P; Pasti. C C; Pulidori. F F; R...
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