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Yuanshu Zhang - One of the best experts on this subject based on the ideXlab platform.
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Effect of #beta#-Casomorphin-7 on immunityt in rats
Animal Husbandry & Veterinary Medicine, 2020Co-Authors: Wenhua Zhou, Weihua Chen, Yuanshu ZhangAbstract:This experiment demonstrated that feeding rats #beta#-Casomorphins to some extent enhanced immunity of them.
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beta Casomorphin 7 prevents epithelial mesenchymal transdifferentiation of nrk 52e cells at high glucose level involvement of angii tgf β1 pathway
Peptides, 2015Co-Authors: Wei Zhang, Shangxin Song, Yuanshu ZhangAbstract:Abstract Background Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, β-Casomorphin-7 may exert anti-fibrotic activities in diabetic rats. However, the role of β-Casomorphin-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, this study was designed to investigate the protective effect of β-Casomorphin-7 on epithelial-mesenchymal transition (EMT) of NRK-52E cells treated under hyperglycemic condition and to explore the possible mechanism. Research design and methods NRK-52E cells were cultured in high glucose (30 mM) for 3 days. Different concentrations of β-Casomorphin-7, naloxone (antagonist of opioid receptor) and losartan (antagonist of angiotensin II type I receptor) were added in the culture. Expression of α-smooth muscle actin (α-SMA), E-cadherin, vimentin and cytokeratin19 mRNA were determined by real-time PCR. Protein levels of E-cadherin and α-SMA were analyzed by Western blotting. The concentrations of angiotensin (Ang) II and transforming growth factor β1 (TGF-β1) in the culture medium were determined. Results High glucose-induced up-regulation of vimentin mRNA and α-SMA mRNA and protein were significantly inhibited by β-Casomorphin-7. On the contrary, high glucose-induced down-regulation of cytokeratin19 mRNA and E-cad mRNA and protein was significantly reversed by β-Casomorphin-7. β-Casomorphin-7 significantly alleviate high glucose induced increase of AngII and TGF-β1 in the culture. Moreover, losartan significantly attenuated the expression of TGF-β1 and EMT of NRK-52E cells treated under hyperglycemic condition. But naloxone did not affect the EMT of NRK-52E cells treated by high glucose and β-Casomorphin-7. Conclusion We demonstrate that β-Casomorphin-7 has the potential to inhibit high glucose-induced renal proximal tubular EMT partly by modulating AngII-TGF-β1 pathway, but not by opioid receptor.
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β Casomorphin 7 attenuates the development of nephropathy in type i diabetes via inhibition of epithelial mesenchymal transition of renal tubular epithelial cells
Peptides, 2012Co-Authors: Wei Zhang, Jinfeng Miao, Yuanshu ZhangAbstract:Abstract This study was designed to investigate the putative protective effect of β-Casomorphin-7 on diabetic nephropathy in a rat model, and to explore the possible mechanism of this effect. SD rats were randomly divided into the following three groups: control group, diabetes group and β-Casomorphin-7-treatment group. All rats were euthanized after 30 days with or without β-Casomorphin-7 treatment. Biochemical parameters including blood glucose and renal function were quantified. The concentration of plasma TGF-β1 was measured by ELISA. Histopathological changes to the kidney were studied by Masson and Sirius red staining. Expressions of α-smooth muscle actin (α-SMA), E-cadherin, vimentin, cytokeratin19 and TGF-β1 mRNA in rat renal cortices were analyzed by real-time PCR. Changes in α-SMA and E-cadherin protein expression in rat renal cortices were quantified by Western blot. β-Casomorphin-7 treatment of diabetic rats reduced urinary glucose, urinary protein, serum creatinine, blood urinary nitrogen, plasma TGF-β1 and the ratio of kidney: body weight. Masson and Sirius red staining showed that β-Casomorphin-7 treatment attenuated renal interstitial fibrosis in diabetic rats. Compared to the control rats, diabetic rats had elevated expressions of α-SMA, vimentin and TGF-β1 mRNA and α -SMA protein and decreased expression of E-cadherin and cytokeratin19 mRNA, and E-cadherin protein. β-Casomorphin-7 treatment of diabetic rats partially normalized these changes. Our results suggest that administration of β-Casomorphin-7 attenuates renal interstitial fibrosis caused by diabetes. This protective effect may be associated, in part, with down regulation of epithelial–mesenchymal transition of renal tubular epithelial cells.
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β-Casomorphin-7 attenuates the development of nephropathy in type I diabetes via inhibition of epithelial–mesenchymal transition of renal tubular epithelial cells
Peptides, 2012Co-Authors: Wei Zhang, Jinfeng Miao, Chang Ma, Yuanshu ZhangAbstract:Abstract This study was designed to investigate the putative protective effect of β-Casomorphin-7 on diabetic nephropathy in a rat model, and to explore the possible mechanism of this effect. SD rats were randomly divided into the following three groups: control group, diabetes group and β-Casomorphin-7-treatment group. All rats were euthanized after 30 days with or without β-Casomorphin-7 treatment. Biochemical parameters including blood glucose and renal function were quantified. The concentration of plasma TGF-β1 was measured by ELISA. Histopathological changes to the kidney were studied by Masson and Sirius red staining. Expressions of α-smooth muscle actin (α-SMA), E-cadherin, vimentin, cytokeratin19 and TGF-β1 mRNA in rat renal cortices were analyzed by real-time PCR. Changes in α-SMA and E-cadherin protein expression in rat renal cortices were quantified by Western blot. β-Casomorphin-7 treatment of diabetic rats reduced urinary glucose, urinary protein, serum creatinine, blood urinary nitrogen, plasma TGF-β1 and the ratio of kidney: body weight. Masson and Sirius red staining showed that β-Casomorphin-7 treatment attenuated renal interstitial fibrosis in diabetic rats. Compared to the control rats, diabetic rats had elevated expressions of α-SMA, vimentin and TGF-β1 mRNA and α -SMA protein and decreased expression of E-cadherin and cytokeratin19 mRNA, and E-cadherin protein. β-Casomorphin-7 treatment of diabetic rats partially normalized these changes. Our results suggest that administration of β-Casomorphin-7 attenuates renal interstitial fibrosis caused by diabetes. This protective effect may be associated, in part, with down regulation of epithelial–mesenchymal transition of renal tubular epithelial cells.
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protective effect of β Casomorphin 7 on type 1 diabetes rats induced with streptozotocin
Peptides, 2010Co-Authors: Jinfeng Miao, Yuanshu ZhangAbstract:Abstract The present study was aimed to investigate the possible effects of β-Casomorphin-7, against hyperglycemia and free radical-mediated oxidative stress in streptozotocin-induced diabetic rats by assaying the blood glucose level and the activity of plasma enzymatic antioxidants, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px). A significant increase in the levels of both blood glucose and oxidative stress with a predominant decrease in antioxidant status was observed in the diabetic rats when compared to control rats. After 15 days oral administration of β-Casomorphin-7 (7.5 × 10 −8 mol/day), the elevated blood glucose level was reduced. Oral administration of β-CM-7 to diabetic rats showed an increase in the level of plasma insulin, the elevated plasma glucagon level was markedly reduced by the oral administration of β-CM-7. Oral administration of β-CM-7 to the diabetic group of rats also showed a significant elevation in the activity of SOD and catalase. Thus, the results of the present study suggest that β-Casomorphin-7 can protect rats from hyperglycemia and free radical-mediated oxidative stress in diabetic rats.
Elias Castanas - One of the best experts on this subject based on the ideXlab platform.
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Receptorphin: A conserved peptide derived from the sequence of the opioid receptor, with opioid displacement activity and potent antiproliferative actions in tumor cells
BMC Pharmacology, 2001Co-Authors: Marilena Kampa, Spyros Loukas, Andreas Tsapis, Elias CastanasAbstract:Background In addition to endogenous opioids, a number of peptide sequences, derived from endogenous (hemorphins, alphaS1-Casomorphin), and exogenous proteins (Casomorphins, exorphins) have been reported, possessing opioid activity. In the present work, we report the identification of a new peptide, receptorphin (Tyr-Ile-Phe-Asn-Leu), derived from the sequence of the second transmembrane loop of the opioid receptor. This sequence is unique for the opioid receptor, and conserved in all species and receptor-types. Results and Discussion Receptorphin competes for opioid binding, presenting a kappa-receptor interaction, while it binds equally to delta- and mu- opioid and somatostatin-binding sites, and inhibits the cell proliferation of a number of human cancer cell lines, in a dose-dependent and reversible manner, at the picomolar or the nanomolar range. Receptorphin shows a preferential action on prostate cancer cells. Conclusion Our work identifies, for the first time a peptide, in a receptor sequence, possessing ligand-agonistic activities. A hypothesis, based on receptorphin liberation after cell death, is presented, which could tentatively explain the time-lag observed during opioid antiproliferative action.
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opioid alkaloids and Casomorphin peptides decrease the proliferation of prostatic cancer cell lines lncap pc3 and du145 through a partial interaction with opioid receptors
European Journal of Pharmacology, 1997Co-Authors: M Kampa, Anastassia Hatzoglou, Pierremarie Martin, Elias Castanas, Efstathia Bakogeorgou, Athina DamianakiAbstract:Opioid agonists (ethylketocyclazocine, etorphine, [d-Ala2,d-Leu5]enkephalin (DADLE), [[d-Ala2,N-Me–Phe4–Gly-ol]enkephalin (DAGO), [d-Ser2,Leu5]enkephalin–Thr6 (DSLET) and morphine were found to inhibit the proliferation of human prostate cancer cell lines (LNCaP, DU145, and PC3), in a dose-dependent manner. The 50% inhibitory concentrations (IC50) were in the picomolar range. In many cases, this effect was antagonized by the general opioid antagonist, diprenorphine, indicating the existence of specific opioid binding sites. Saturation binding experiments with selective ligands and effectors showed no opioid sites on the LNCaP cell line κ1 and μ sites on the PC3 cell line, and κ1, κ3 and μ sites on the DU145 cell line. In other cases, the opioid effect was not antagonized by diprenorphine, indicating that the action of opioids might be mediated through other membrane receptors. Furthermore, Casomorphin peptides, issued from bovine alpha- (alpha-casein-90-95 and alpha-casein-90-96) and beta-caseins (beta-Casomorphin and beta-Casomorphin-1-5), and human alphaS1-casein (alphaS1-Casomorphin and alphaS1-Casomorphin amide) inhibited cell proliferation of human prostate cell lines, also by a mechanism partly involving opioid receptors. As opioid neurons can be found in the prostate gland, and Casomorphin peptides might reach the gland through the general circulation, the above findings indicate a putative role of opioids in prostate cancer cell growth.
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identification of a novel opioid peptide tyr val pro phe pro derived from human alpha s1 casein alpha s1 Casomorphin and alpha s1 Casomorphin amide
Biochemical Journal, 1996Co-Authors: M Kampa, Spyros Loukas, Anastassia Hatzoglou, Patrice Martin, Pierremarie Martin, Elias CastanasAbstract:: A new Casomorphin pentapeptide (alpha S1-Casomorphin) has been isolated from the sequence of human alpha S1-casein [alpha S1-casein-(158-162)], with the sequence Tyr-Val-Pro-Phe-Pro. This peptide was found to bind with high affinity to all three subtypes of the kappa-opioid receptor (kappa 1-kappa 2). When amidated at the C-terminus, alpha S1-Casomorphin amide binds to the delta- and kappa 3-opioid sites. Both alpha S1-Casomorphin and its amide inhibit in a dose-dependent and reversible manner the proliferation of T47D human breast cancer cells. This anti-proliferative activity was greater for alpha S1-Casomorphin, which was the most potent opioid in inhibiting T47D cell proliferation. In T47D breast cancer cells, other Casomorphins have been found to bind to somatostatin receptors in addition to opioid sites. In contrast, alpha S1-Casomorphin and its amide do not interact with somatostatin receptors in our system.
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Antiproliferative and receptor binding properties of α- and β-Casomorphins in the T47D human breast cancer cell line
European Journal of Pharmacology, 1996Co-Authors: Anastassia Hatzoglou, Pierremarie Martin, Efstathia Bakogeorgou, Chryssa Hatzoglou, Elias CastanasAbstract:In previous studies, we have shown that opioid agonists ([d-Ala2,d-Leu5]enkephalin (DADLE), [d-Ser2,Leu5]enkephalin-Thr6 (DSLET), ethylketocyclazocine and etorphine) bind to opioid binding sites and decrease cell proliferation of human T47D breast cancer cells. Furthermore, we provided evidence about a cross-reaction, also in the T47D human breast cancer cell line, of μ-acting opioids with type-II somatostatin receptors. Since a potential source of opioid activity in the breast might be Casomorphin peptides (produced by the enzymatic degradation of α-casein and β-casein), we investigated the antiproliferative action of five different Casomorphin peptides: α-casein-(90–95), α-casein-(90–96), β-Casomorphin, β-Casomorphin-(1–5) and morphiceptin. We show that all five peptides decreased, in a dose-dependent manner, cell proliferation. The general antagonist diprenorphine produced only a partial reversal of their action. Furthermore, we provide evidence that all peptides (except for morphiceptin) bind to δ- and κ-opioid binding sites of T47D cells with different selectivity. Finally, we show that these peptides are also partial competitors at the somatostatin receptors present in the same cell line.
Pascale Plaisancie - One of the best experts on this subject based on the ideXlab platform.
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β Casomorphin 7 regulates the secretion and expression of gastrointestinal mucins through a μ opioid pathway
American Journal of Physiology-gastrointestinal and Liver Physiology, 2006Co-Authors: Sandra Zoghbi, Jean Claustre, Gérard Jourdan, Aurelien Trompette, Mahmoud El Homsi, Javier Garzon, Jeanyves Scoazec, Pascale PlaisancieAbstract:We have recently shown that β-Casomorphin-7, a milk opioid peptide, strongly stimulates mucin secretion in the rat jejunum through a nervous pathway and opioid receptor activation. In this study, t...
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Milk Bioactive Peptides and β-Casomorphins Induce Mucus Release in Rat Jejunum
Journal of Nutrition, 2003Co-Authors: Aurelien Trompette, Fabienne Caillon, Jean Claustre, Gérard Jourdan, Jean-alain Chayvialle, Pascale PlaisancieAbstract:: Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and beta-Casomorphin-7, a mu-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter mu-opioid peptides have been described, the effects of the opioid peptides in casein, beta-Casomorphin-7, -6, -4, -4NH2 and -3, and of opioid neuropeptides met-enkephalin, dynorphin A and (D-Ala2,N-Me-Phe4,glycinol5)enkephalin (DAMGO) on intestinal mucus secretion were investigated. The experiments were conducted with isolated perfused rat jejunum. Mucus secretion under the influence of beta-Casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of beta-Casomorphin-7 (1.2 x 10(-4) mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal beta-Casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of beta-Casomorphin-4 (1.2 x 10(-6) mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide beta-Casomorphin-3 did not release mucus. Among the opioid neuropeptides, intra-arterial infusion of Met-enkephalin or dynorphin-A did not provoke mucus secretion. In contrast, beta-endorphin (1.2 x 10(-8) to 1.2 x 10(-6) mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls). DAMGO (1.2 x 10(-6) mol/L), a mu-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that mu-opioid neuropeptides, as well as beta-Casomorphins after absorption, modulate intestinal mucus discharge. Milk opioid-derived peptides may thus be involved in defense against noxious agents and could have dietary and health applications.
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Milk bioactive peptides and beta-Casomorphins induce mucus release in rat jejunum.
The Journal of nutrition, 2003Co-Authors: Aurelien Trompette, Fabienne Caillon, Jean Claustre, Gérard Jourdan, Jean-alain Chayvialle, Pascale PlaisancieAbstract:Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and beta-Casomorphin-7, a mu-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter mu-opioid peptides have been described, the effects of the opioid peptides in casein, beta-Casomorphin-7, -6, -4, -4NH2 and -3, and of opioid neuropeptides met-enkephalin, dynorphin A and (D-Ala2,N-Me-Phe4,glycinol5)enkephalin (DAMGO) on intestinal mucus secretion were investigated. The experiments were conducted with isolated perfused rat jejunum. Mucus secretion under the influence of beta-Casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of beta-Casomorphin-7 (1.2 x 10(-4) mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal beta-Casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of beta-Casomorphin-4 (1.2 x 10(-6) mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide beta-Casomorphin-3 did not release mucus. Among the opioid neuropeptides, intra-arterial infusion of Met-enkephalin or dynorphin-A did not provoke mucus secretion. In contrast, beta-endorphin (1.2 x 10(-8) to 1.2 x 10(-6) mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls). DAMGO (1.2 x 10(-6) mol/L), a mu-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that mu-opioid neuropeptides, as well as beta-Casomorphins after absorption, modulate intestinal mucus discharge. Milk opioid-derived peptides may thus be involved in defense against noxious agents and could have dietary and health applications.
Fred Nyberg - One of the best experts on this subject based on the ideXlab platform.
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enhanced levels of immunoreactive β Casomorphin 8 in milk of breastfeeding women with mastitis
Peptides, 2014Co-Authors: Lennart Righard, Anna Carlssonjonsson, Fred NybergAbstract:Abstract An incorrect, superficial suckling technique in breastfeeding frequently leads to milk congestion and sometimes mastitis. In the present study we have examined whether milk congestion may affect levels of the atypical opioid β-Casomorphin-8 in milk and in plasma. We also investigated whether the rate of acute psychosis during the first half year after parturition has declined in Sweden over the years. Milk and plasma samples were collected for peptide analysis from 14 women with mastitis and 10 controls. We found that in a group of 14 late cases of mastitis (median 48 days post partum) the detected mean level of β-Casomorphin-8 in milk was significantly higher and somewhat higher in plasma at the acute stage compared with 2–3 weeks later, after recovery when the symptoms had disappeared, as well as compared to the control subjects. Swedish official statistics show that the incidence of acute psychosis in the first month and in the first half year after birth has declined by a half during the last 30 years. A relationship between postpartum psychosis and elevated β-Casomorphin-8 levels in CSF has been suggested from earlier studies. In this study, milk congestion led to enhanced levels of β-Casomorphin-8 in milk, which may be related to postpartum psychosis and probably also to ‘the postnatal blues’.
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Casomorphins and Hemorphins—Opioid Active Peptides Released by Partial Hydrolysis of Structural Proteins
Handbook of Biologically Active Peptides, 2007Co-Authors: Fred NybergAbstract:ABSTRACT In addition to the classic opioid peptides (β-endorphin, dynorphins, and enkephalins), with the N-terminal Tyr-Gly-Gly-Phe tetrapeptide sequence, opioid active peptides containing the Tyr-Pro dipeptide residues in their N-terminal sequence have been identified and characterized. Other than the endomorphins, these so-called atypical opioid peptides are derived by partial hydrolysis of endogenous existing functional proteins and are mainly produced in peripheral tissues and body fluids. Among the atypical endogenously produced opioid active peptides are the β-Casomorphins and the hemorphins. These peptides are formed through the hydrolysis of the milk protein β-casein and hemoglobin, respectively, and many of their biological effects have been characterized. They are less potent than the classic peptides but share most of their typical opioid effects. Moreover, the detected concentrations of β-Casomorphins and hemorphins in body fluids highly exceed those of the β-endorphin and enkephalins. Originally, the β-Casomorphins and the hemorphins were isolated from enzymatically treated bovine milk and blood, respectively. Later they were identified as naturally occurring compounds in human plasma and cerebrospinal fluid. This chapter gives a brief review of past and current research on the β-Casomorphins and hemorphins regarding the mechanisms for their release, their distribution, their biological actions, and their pathophysiological roles.
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micropurification and amino acid sequence of β Casomorphin 8 in milk from a woman with postpartum psychosis
Peptides, 1993Co-Authors: Staffan Renlund, Inger Erlandsson, Ulf Hellman, Jerzy Silberring, Christer Wernstedt, Leif Lindstrom, Fred NybergAbstract:Abstract Milk was obtained from a woman with acute postpartum psychosis and with ongoing lactation. Defatted samples were subjected to micropurification and collected fractions were analyzed by means of their β-Casomorphin-8 immunoreactivity. Immunoreactive material with the same chromatographic properties as synthetic human β-Casomorphin-8 was determined by amino acid sequence analysis to be Tyr-Pro-Phe-Val-Glu-Pro-Ile-Pro. Its molecular mass was determined by fast atom bombardment-mass spectrometry to be 962.3 Da. These determinations, which ultimately identify the immunoreactive material as human β-Casomorphin-8, represent the first structural identification of a β-Casomorphin peptide from a body fluid.
Anastassia Hatzoglou - One of the best experts on this subject based on the ideXlab platform.
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opioid alkaloids and Casomorphin peptides decrease the proliferation of prostatic cancer cell lines lncap pc3 and du145 through a partial interaction with opioid receptors
European Journal of Pharmacology, 1997Co-Authors: M Kampa, Anastassia Hatzoglou, Pierremarie Martin, Elias Castanas, Efstathia Bakogeorgou, Athina DamianakiAbstract:Opioid agonists (ethylketocyclazocine, etorphine, [d-Ala2,d-Leu5]enkephalin (DADLE), [[d-Ala2,N-Me–Phe4–Gly-ol]enkephalin (DAGO), [d-Ser2,Leu5]enkephalin–Thr6 (DSLET) and morphine were found to inhibit the proliferation of human prostate cancer cell lines (LNCaP, DU145, and PC3), in a dose-dependent manner. The 50% inhibitory concentrations (IC50) were in the picomolar range. In many cases, this effect was antagonized by the general opioid antagonist, diprenorphine, indicating the existence of specific opioid binding sites. Saturation binding experiments with selective ligands and effectors showed no opioid sites on the LNCaP cell line κ1 and μ sites on the PC3 cell line, and κ1, κ3 and μ sites on the DU145 cell line. In other cases, the opioid effect was not antagonized by diprenorphine, indicating that the action of opioids might be mediated through other membrane receptors. Furthermore, Casomorphin peptides, issued from bovine alpha- (alpha-casein-90-95 and alpha-casein-90-96) and beta-caseins (beta-Casomorphin and beta-Casomorphin-1-5), and human alphaS1-casein (alphaS1-Casomorphin and alphaS1-Casomorphin amide) inhibited cell proliferation of human prostate cell lines, also by a mechanism partly involving opioid receptors. As opioid neurons can be found in the prostate gland, and Casomorphin peptides might reach the gland through the general circulation, the above findings indicate a putative role of opioids in prostate cancer cell growth.
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identification of a novel opioid peptide tyr val pro phe pro derived from human alpha s1 casein alpha s1 Casomorphin and alpha s1 Casomorphin amide
Biochemical Journal, 1996Co-Authors: M Kampa, Spyros Loukas, Anastassia Hatzoglou, Patrice Martin, Pierremarie Martin, Elias CastanasAbstract:: A new Casomorphin pentapeptide (alpha S1-Casomorphin) has been isolated from the sequence of human alpha S1-casein [alpha S1-casein-(158-162)], with the sequence Tyr-Val-Pro-Phe-Pro. This peptide was found to bind with high affinity to all three subtypes of the kappa-opioid receptor (kappa 1-kappa 2). When amidated at the C-terminus, alpha S1-Casomorphin amide binds to the delta- and kappa 3-opioid sites. Both alpha S1-Casomorphin and its amide inhibit in a dose-dependent and reversible manner the proliferation of T47D human breast cancer cells. This anti-proliferative activity was greater for alpha S1-Casomorphin, which was the most potent opioid in inhibiting T47D cell proliferation. In T47D breast cancer cells, other Casomorphins have been found to bind to somatostatin receptors in addition to opioid sites. In contrast, alpha S1-Casomorphin and its amide do not interact with somatostatin receptors in our system.
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Antiproliferative and receptor binding properties of α- and β-Casomorphins in the T47D human breast cancer cell line
European Journal of Pharmacology, 1996Co-Authors: Anastassia Hatzoglou, Pierremarie Martin, Efstathia Bakogeorgou, Chryssa Hatzoglou, Elias CastanasAbstract:In previous studies, we have shown that opioid agonists ([d-Ala2,d-Leu5]enkephalin (DADLE), [d-Ser2,Leu5]enkephalin-Thr6 (DSLET), ethylketocyclazocine and etorphine) bind to opioid binding sites and decrease cell proliferation of human T47D breast cancer cells. Furthermore, we provided evidence about a cross-reaction, also in the T47D human breast cancer cell line, of μ-acting opioids with type-II somatostatin receptors. Since a potential source of opioid activity in the breast might be Casomorphin peptides (produced by the enzymatic degradation of α-casein and β-casein), we investigated the antiproliferative action of five different Casomorphin peptides: α-casein-(90–95), α-casein-(90–96), β-Casomorphin, β-Casomorphin-(1–5) and morphiceptin. We show that all five peptides decreased, in a dose-dependent manner, cell proliferation. The general antagonist diprenorphine produced only a partial reversal of their action. Furthermore, we provide evidence that all peptides (except for morphiceptin) bind to δ- and κ-opioid binding sites of T47D cells with different selectivity. Finally, we show that these peptides are also partial competitors at the somatostatin receptors present in the same cell line.