- GHK Resets COPD Genes
- GHK and Lung Regrowth
- Extra Copper May Diminish COPD
- Low Copper Increased COPD
NEW LUNG RESEARCH ON GHK!
Oncotarget. 2016 Aug 10. doi: 10.18632/oncotarget.11168. [Epub ahead of print]
The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice.
Park JR1,2, Lee H1, Kim SI3, Yang SR1.
The tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu (II) (GHK-Cu) is involved in wound healing and tissue remodeling. Although GHK-Cu exhibits anti-aging and tissue renewing properties, its roles in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are still unknown. Therefore, we examined the effects of GHK-Cu in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro and ALI in mice in vivo.GHK-Cu treatment reduced reactive oxygen species (ROS) production, increased superoxide dismutase (SOD) activity while decreased TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling in vitro and in vivo model of ALI. Moreover, GHK-Cu attenuated LPS-induced lung histological alterations, suppressed the infiltration of inflammatory cells into the lung parenchyma in LPS-induced ALI in mice. Taken together, these findings demonstrate that GHK-Cu possesses a protective effect in LPS-induced ALI by inhibiting excessive inflammatory responses; accordingly it may represent a novel therapeutic approach for ALI/ARDS.
KEYWORDS: GHK-Cu; NF-κB p65; acute lung injury; inflammation; p38 MAPK
PMID: 27517151 DOI: 10.18632/oncotarget.11168 [PubMed - as supplied by publisher] Free full text
Copper Peptide Chelator GHK
Resets Emphysema COPD Genes to Health
This information is for the use of medical researchers and persons interested in health sciences. It must be emphasized that GHK and other copper binding peptides have not been tested on human emphysema and COPD and are not approved for such uses.
Emphysema and attendant lung disease is the 2rd leading cause of death in the world. It is a deadly and painful disease of the lungs that causes difficulty in breathing. In people with emphysema, the tissues necessary to support the physical shape and function of the lungs are destroyed. Emphysema is most often caused by tobacco smoking and long-term exposure to air pollution. Emphysema is also a component of normal aging. As the lungs get older, the elastic properties decrease, and the tensions that develop can result in areas of emphysema.
In the study below, it was found that GHK, at a very low concentration (10 nanomolar) reversed the effects of emphysema on the genes of affected fibroblast cells from the patients. GHK shut down tissue destructive genes and increased genes that control wound repair and tissue remodeling.
Persons with severe emphysema use air inhalation systems that pump misty, water-filled air in and out of the lungs. Often steroids are added to the solution to suppress the lung inflammation, but while this provides short-term help, it also inhibits lung repair. In theory, GHK could be infused into the blood stream of patients to repair the lung tissue. In our wound healing studies we found that GHK-copper induced accelerated systemic healing through rats, mice , and pigs. Or it could be added to the misting solution or used in combination of a carrier like DMSO along with GHK in the misting solution. DMSO and GHK or GHK-copper always worked well together on wound healing.
Any experiments done along these suggested approaches should only be performed by qualified medical researchers.
The full article is available at no cost at www.genomemedicine.com/content/4/8/67.
Next-generation personalized drug discovery: the tripeptide GHK hits center stage in chronic obstructive pulmonary disease.
Meiners S, Eickelberg O. Genome Med. 2012 Sep 21;4(8):70. ABSTRACT Chronic lung diseases (CLDs), including chronic obstructive pulmonary disease (COPD), are the second leading cause of death worldwide. The first report of database-driven drug discovery in carefully phenotyped COPD specimens has now been published in Genome Medicine, combining gene expression data in defined emphysematous areas with connectivity-map-based compound discovery. This joint effort may lead the way to novel and potentially more efficient concepts of personalized drug discovery for COPD in particular, and CLD in general.
A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK.
Campbell JD, McDonough JE, Zeskind JE, Hackett TL, Pechkovsky DV, Brandsma CA, Suzuki M, Gosselink JV, Liu G, Alekseyev YO, Xiao J, Zhang X, Hayashi S, Cooper JD, Timens W, Postma DS, Knight DA, Lenburg ME, Hogg JC, Spira A. Genome Med. 2012 Aug 31;4(8):67.Genome Med. 2012 Aug 31;4(8):67. [Epub ahead of print]
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease consisting of emphysema, small airway obstruction, and/or chronic bronchitis that results in significant loss of lung function over time.
METHODS: In order to gain insights into the molecular pathways underlying progression of emphysema and explore computational strategies for identifying COPD therapeutics, we profiled gene expression in lung tissue samples obtained from regions within the same lung with varying amounts of emphysematous destruction from smokers with COPD (8 regions x 8 lungs = 64 samples). Regional emphysema severity was quantified in each tissue sample using the mean linear intercept (Lm) between alveolar walls from micro-CT scans.
RESULTS: We identified 127 genes whose expression levels were significantly associated with regional emphysema severity while controlling for gene expression differences between individuals. Genes increasing in expression with increasing emphysematous destruction included those involved in inflammation, such as the B-cell receptor signaling pathway, while genes decreasing in expression were enriched in tissue repair processes, including the transforming growth factor beta (TGF beta) pathway, actin organization, and integrin signaling. We found concordant differential expression of these emphysema severity-associated genes in four cross-sectional studies of COPD. Using the Connectivity Map, we identified GHK as a compound that can reverse the gene-expression signature associated with emphysematous destruction and induce expression patterns consistent with TGF beta pathway activation. Treatment of human fibroblasts with GHK recapitulated TGF beta-induced gene-expression patterns, led to the organization of the actin cytoskeleton, and elevated the expression of integrin beta1. Furthermore, addition of GHK or TGF beta restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs compared to fibroblasts from former smokers without COPD.
CONCLUSIONS: These results demonstrate that gene-expression changes associated with regional emphysema severity within an individual's lung can provide insights into emphysema pathogenesis and identify novel therapeutic opportunities for this deadly disease. They also suggest the need for additional studies to examine the mechanisms by which TGF beta and GHK each reverse the gene-expression signature of emphysematous destruction and the effects of this reversal on disease progression.
It is also possible that GHK may improve lung regrowth in patients with COPD.
Exp Lung Res. 1986;10(2):115-36.
The effect of culture conditions on cytodifferentiation of fetal mouse lung respiratory passageways.
Hilfer SR, Schneck SL, Brown JW.
Differentiation of the respiratory region of fetal mouse lungs was investigated in serum-free medium supplemented with growth factors and hormones. Terminal buds from the margins of a lobe were removed from 16-day fetuses and organ cultures prepared either in submersion culture or at the air-medium interface. It was found that glycyl-L-histidyl-L-lysine, transferrin, and somatostatin were sufficient to promote branching in the absence of serum. However, type II pneumocytes containing lamellar bodies formed only in the presence of thyroxine or dexamethasone. At concentrations of these hormones slightly above the physiological range most of the cells became cuboidal and contained lamellar bodies; at lower concentrations regions of flattened cells appeared. In submersion culture a large, central cavity surrounded by saccules was formed rather than a branched tree. Thus, the pattern of differentiation is significantly influenced by culture conditions.
Just extra copper may help diminish COPD
I am a biochemist and not a physician. So always clear any advice from me with your physician.
GHK is not available in hospitals. What may help in COPD is to have the patient take 6 mgs of copper 2+ a day as copper glycinate. Take it after a meal. The 6 mgs number came from human studies by the US Department of Agriculture that found this level produced the most anti-oxidant activity in human blood.
All of our studies indicated that GHK acts as a copper complex. We were never able to obtain strong healing without added copper. And a copper chelator, bathocuproine, would stop GHK effects in cell culture.
Taking more nutritional copper will add more copper to the GHK in body and may help. Most GHK in a person's body does not have copper. The blood protein albumin and GHK have about equal binding to copper 2+. But there are about 1,000 albumin molecules for each GHK in the blood, so GHK may have difficulty obtaining its copper. Thus adding more dietary copper may help create more biologically active GHK.
And also take some supplemental zinc. Too much copper will drive out zinc which is also needed by your body.
There is a recommendation of a 7 to 1, zinc to copper ratio. I believe 4 to 1 would be better. So for 6 mgs of copper, take about 24 mg zinc. A person might have to search for best personal ratio of zinc to copper.
Below is information on one woman that this may have helped. I had recommended giving the woman in Guatemala the 6 mgs of copper glycinate and use GHK-copper on her chest near her lungs, and I think this is what helped.
Evidence that low copper increases COPD
PLoS One. 2012;7(1):e30678. doi: 10.1371/journal.pone.0030678. Epub 2012 Jan 20. Copper deficiency induced emphysema is associated with focal adhesion kinase inactivation. Mizuno S, Yasuo M, Bogaard HJ, Kraskauskas D, Alhussaini A, Gomez-Arroyo J, Farkas D, Farkas L, Voelkel NF.
Source Pulmonary and Critical Care Medicine Division and Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, Virginia, United States of America.
BACKGROUND: Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1α) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein cross-linking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK).
METHODOLOGY: To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA). PRINCIPAL FINDINGS: Copper depletion caused emphysematous changes, decreased HIF-1α activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim.
CONCLUSIONS: These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema, which may be associated with decreased HIF-1α and FAK activity in the lung. .............
Chest. 1984 Jun;85(6 Suppl):70S-73S. Mechanisms of lung injury in the copper-deficient hamster model of emphysema. Soskel NT, Watanabe S, Sandberg LB.
Nutr Rev. 1983 Oct;41(10):318-20. Copper deficiency and developmental emphysema. No authors or abstract listed.
Am Rev Respir Dis. 1982 Aug;126(2):312-5. The relationship of pulmonary function to copper concentrations in drinking water. Sparrow D, Silbert JE, Weiss ST.
Copper has been shown to be an important cofactor for certain enzymatic reactions. Specifically, cross-linking of elastin is inhibited by copper deficiency. In animal models, this inhibition leads to weakened connective tissue and pathologic changes in the lungs consistent with emphysema. To explore the potential relationship of copper exposure to level of pulmonary function in humans, we examined copper concentrations in tap water in the homes of 297 adult male subjects involved in the Normative Aging Study. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were obtained by standard techniques. The relationship of tap water copper concentration to pulmonary function was explored using multiple regression analysis, controlling for other potential confounding variables (age, height, smoking status, and educational attainment). Separate regressions were performed for each of 3 smoking status groups: never, former, and current. Among never smokers, tap water copper was significantly and positively related to levels of both FVC (p = 0.014) and FEV1 (p = 0.027). No significant trend was found among former or current smokers. These data suggest that copper intake may be an important determinant of level of pulmonary function and deserves further investigation.
Am Rev Respir Dis. 1982 Aug;126(2):316-25. A copper-deficient, zinc-supplemented diet produces emphysema in pigs. Soskel NT, Watanabe S, Hammond E, Sandberg LB, Renzetti AD Jr, Crapo JD.
A mild form of emphysema was produced in pigs raised on a copper-deficient, zinc-supplemented diet. The copper-requiring enzyme, lysyl oxidase, catalyzes the cross-linking of tropoelastin into mature elastin. Zinc further inhibits the activity of lysyl oxidase. Lungs from animals raised on copper-deficient, zinc-supplemented diets of demonstrate perforations in alveolar walls and diminished amounts of elastin bronchi and pulmonary arteries. Mean linear intercepts are greater and alveolar internal surface areas are less than those in control animals, fulfilling the generally accepted definition of emphysema. Physiologic confirmation is provided by a leftward shift of the saline volume-pressure curves when compared with those in control animals. Ultrastructurally, the alveolar walls are effaced and pores of Kohn are enlarged. There are areas in which elastin is absent leaving remnant microfibrils, and there are other changes consistent with active elastin synthesis. Biochemical data demonstrate no difference in elastin content as micrograms/ml of fat-free dry weight but do demonstrate increased collagen content in experimental animal lungs compared with that in control lungs. Ultrastructural similarities to enzyme-induced models of emphysema suggest the presence of elastin degradation in our model. We speculate that although the copper-deficient, zinc-supplemented state may stimulate protein synthesis in general, elastin is being degraded by endogenous means, but collagen is not.
Am J Pathol. 1978 Jun;91(3):413-32. The lung of the copper-deficient rat. A model for developmental pulmonary emphysema. O'Dell BL, Kilburn KH, McKenzie WN, Thurston RJ.
Based on the hypothesis that cross-linked elastin is critical for normal lung structure, lung tissue from copper-deficient rats was studied. Copper deficiency was induced in the second generation by feeding dams a milk-based diet low in copper (less than 1 ppm) during gestation and lactation. The weanlings were fed the same diet until they showed severe signs of deficiency between 6 and 10 weeks of age. Controls animals received the basal diet supplemented with 10 ppm copper. Liver cytochrome oxidase activity, which served as the chief index of deficiency, decreased from a normal level of approximately 80 to 15 mumole/min/g. The lungs of the deficient animals contained 17% less elastin and had 35% larger alveolar spaces (34.7 vs 47.7 intercepts), as determined by the mean alveolar intercept method. The ultrastructure of elastin in the bronchi, arterioles, and alveolar ducts had a "washed out" appearance. To determine the reversibility of the pathology, deficient animals, 5 to 10 weeks of age, were repleted by feeding a copper-supplemented diet for 1, 2, and 3 months. During this period growth resumed, anemia disappeared, and liver cytochrome oxidase returned to normal. There was no improvement in lung structure with regard to alveolar size (28.4 intercepts compared with 43.6 in controls and 35.1 in deficient littermates killed at the start of repletion). The ultrastructure and electron density of pulmonary elastin was restored to near normal. The lung of the copper-deficient rat is proposed as a model for developmental pulmonary emphysema.