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Lorraine Pariset - One of the best experts on this subject based on the ideXlab platform.
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comparison of Milk fat globule membrane mfgm proteins in Milk samples of chianina and holstein cattle breeds across three lactation phases through 2d ief sds page a preliminary study
Food Research International, 2013Co-Authors: Leonardo Murgiano, A. Valentini, Lello Zolla, Angelo Dalessandro, Lorraine ParisetAbstract:Abstract Background Characterisation and identification of proteins involved in Milk production are important to understand the biology of lactation and to manage dairy cattle selection. Many studies have investigated mammary function, Milk Secretion and mammary gland involution, but the critical molecular mechanisms implicated are still incomplete. We focused on Milk Fat Globule Membranes (MFGM), a unique subcategory of proteins mainly originating from the Golgi apparatus and endoplasmic reticulum of mammary gland cells. Methods Using a proteomic approach, 2D-IEF SDS PAGE and ESI MS/MS we compared Milk MFGM belonging to Chianina and Holstein cattle breeds, representative of selection for meat and Milk traits, respectively. Results The two breeds showed different trends in the amount of structural proteins and proteins related to lipid droplet formation, as well as in immunity-related molecules, MFG Secretion, mammary gland epithelium apoptosis and mammary gland involution. Conclusions We successfully isolated the major MFGM proteins and monitored their differences between the two breeds, among three different lactation phases and within the same breed across the lactation phases. The detected differences were relative to the amount of proteins involved in lipid deposition into the droplets, immune system and mammary gland cell apoptosis.
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comparison of Milk fat globule membrane mfgm proteins of chianina and holstein cattle breed Milk samples through proteomics methods
Nutrients, 2009Co-Authors: Leonardo Murgiano, Silvia Bongiorni, A. Valentini, Lello Zolla, Anna Maria Timperio, Lorraine ParisetAbstract:Identification of proteins involved in Milk production is important to understand the biology of lactation. Many studies have advanced the understanding of mammary function and Milk Secretion, but the critical molecular mechanisms implicated in Milk fat Secretion is still incomplete. Milk Fat Globules are secreted from the apical surface of the mammary cells, surrounded by a thin membrane bilayer, the Milk Fat Globule Membrane (MFGM), formed by proteins which have been suggested to be cholesterolemia-lowering factors, inhibitors of cancer cell growth, vitamin binders, bactericidal, suppressors of multiple sclerosis. Using a proteomic approach, we compared MFGM from Milk samples of individuals belonging to two different cattle breeds, Chianina and Holstein, representative of selection for Milk and meat traits, respectively. We were able to isolate some of the major MFGM proteins in the examined samples and to identify differences between the protein fractions of the two breeds. We detected differences in the amount of proteins linked to mammary gland development and lipid droplets formation, as well as host defence mechanisms. We have shown that proteomics is a suitable, unbiased method for the study of Milk fractions proteins and a powerful tool in nutritional genomics.
Gracia Merino - One of the best experts on this subject based on the ideXlab platform.
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effect of bovine abcg2 polymorphism y581s snp on Secretion into Milk of enterolactone riboflavin and uric acid
Animal, 2016Co-Authors: Jon A Otero, Veronica Miguel, L Gonzalezlobato, J G Prieto, Gracia Merino, Rocio Garciavillalba, Juan Carlos Espin, A I AlvarezAbstract:The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and Milk Secretion of endogenous and exogenous compounds, actively affecting Milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the Secretion into Milk of compounds implicated in Milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases Milk Secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and Milk Secretion of compounds such as riboflavin (vitamin B 2 ), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and Milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo . Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into Milk with a two-fold increase in the Milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated Milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the Milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid, which could affect both Milk quality and functionality.
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the bovine atp binding cassette transporter abcg2 tyr581ser single nucleotide polymorphism increases Milk Secretion of the fluoroquinolone danofloxacin
Drug Metabolism and Disposition, 2013Co-Authors: Jon A Otero, J G Prieto, Rebeca Real, A I Alvarez, A. De La Fuente, Margarita M. Marques, Gracia MerinoAbstract:The bovine adenosine triphosphate-binding cassette transporter G2 (ABCG2/breast cancer resistance protein) polymorphism Tyr581Ser (Y581S) has recently been shown to increase in vitro transepithelial transport of antibiotics. Since this transporter has been extensively related to the active Secretion of drugs into Milk, the potential in vivo effect of this polymorphism on Secretion of xenobiotics in livestock could have striking consequences for Milk production, the dairy industry, and public health. Our purpose was to study the in vivo effect of this polymorphism on the Secretion of danofloxacin, a widely used veterinary antibiotic, into Milk. Danofloxacin (1.25 mg/kg) was administered to six Y/Y 581 homozygous and six Y/S 581 heterozygous lactating cows, and plasma and Milk samples were collected and analyzed by high-performance liquid chromatography. No differences were found in the pharmacokinetic parameters of danofloxacin in plasma between the two groups of animals. In contrast, Y/S heterozygous cows showed a 2-fold increase in danofloxacin levels in Milk. In addition, the pharmacokinetic elimination parameters, mean residence time and elimination half-life, were significantly lower in the Milk of the animals carrying the Y/S polymorphism. These in vivo results are in agreement with our previously published in vitro data, which showed a greater capacity of the S581 variant in accumulation assays, and demonstrate, for the first time, an important effect of the Y581S single-nucleotide polymorphism on antibiotic Secretion into cow Milk. These findings could be extended to other ABCG2 substrates, and may be relevant for the treatment of mastitis and for the design of accurate and novel strategies to handle Milk residues.
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multidrug transporter abcg2 breast cancer resistance protein secretes riboflavin vitamin b2 into Milk
Molecular and Cellular Biology, 2007Co-Authors: Antonius E Van Herwaarden, Gracia Merino, Johan W Jonker, Els Wagenaar, Hilde Rosing, Jos H Beijnen, Alfred H. SchinkelAbstract:The multidrug transporter breast cancer resistance protein (BCRP/ABCG2) is strongly induced in the mammary gland during pregnancy and lactation. We here demonstrate that BCRP is responsible for pumping riboflavin (vitamin B2) into Milk, thus supplying the young with this important nutrient. In Bcrp1−/− mice, Milk Secretion of riboflavin was reduced >60-fold compared to that in wild-type mice. Yet, under laboratory conditions, Bcrp1−/− pups showed no riboflavin deficiency due to concomitant Milk Secretion of its cofactor flavin adenine dinucleotide, which was not affected. Thus, two independent Secretion mechanisms supply vitamin B2 equivalents to Milk. BCRP is the first active riboflavin efflux transporter identified in mammals and the first transporter shown to concentrate a vitamin into Milk. BCRP activity elsewhere in the body protects against xenotoxins by reducing their absorption and mediating their excretion. Indeed, Bcrp1 activity increased excretion of riboflavin into the intestine and decreased its systemic availability in adult mice. Surprisingly, the paradoxical dual utilization of BCRP as a xenotoxin and a riboflavin pump is evolutionarily conserved among mammals as diverse as mice and humans. This study establishes the principle that an ABC transporter can transport a vitamin into Milk and raises the possibility that other vitamins and nutrients are likewise secreted into Milk by ABC transporters.
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interaction of enrofloxacin with breast cancer resistance protein bcrp abcg2 influence of flavonoids and role in Milk Secretion in sheep
Journal of Veterinary Pharmacology and Therapeutics, 2006Co-Authors: Mivis M. Pulido, J G Prieto, Gracia Merino, Antonio J. Molina, Gracia Mendoza, Ana I. AlvarezAbstract:The ATP-binding cassette (ABC) transporter breast cancer resistance protein (BCRP)/ABCG2 is a high-capacity efflux transporter with wide substrate specificity located in apical membranes of epithelia, which is involved in drug availability. BCRP is responsible for the active Secretion of clinically and toxicologically important substrates to Milk. The present study shows BCRP expression in sheep and cow by immunoblotting with MAb (BXP-53). Vanadate-sensitive ATPase activity with specific BCRP substrates and inhibitors was measured in bovine mammary gland homogenates. To assess the role of BCRP in ruminant mammary gland we tested the fluoroquinolone enrofloxacin (ENRO). In polarized cell lines, ENRO was transported by Bcrp1/BCRP with secretory/absorptive ratios of 6.5 and 2 respectively. The efflux was blocked by the BCRP inhibitor Ko143. ENRO pharmacokinetics in plasma and Milk was studied in sheep after co-administration of drug (2.5 mg/kg, i.v.) and genistein (0.8 mg/kg, i.m.) or albendazole sulfoxide (2 mg/kg, i.v) as BCRP inhibitors. Concomitant administration of BCRP inhibitors with ENRO had no significant effect on the plasma disposition kinetics of ENRO but decreased ENRO concentrations in Milk.
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breast cancer resistance protein bcrp abcg2 transports fluoroquinolone antibiotics and affects their oral availability pharmacokinetics and Milk Secretion
Drug Metabolism and Disposition, 2006Co-Authors: Gracia Merino, Ana I. Alvarez, Mivis M. Pulido, Antonio J. Molina, Alfred H. Schinkel, Julio G. PrietoAbstract:The breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette drug efflux transporter that extrudes xenotoxins from cells in intestine, liver, mammary gland, and other organs, affecting the pharmacological and toxicological behavior of many compounds, including their Secretion into the Milk. The purpose of this study was to determine whether three widely used fluoroquinolone antibiotics (ciprofloxacin, ofloxacin, and norfloxacin) are substrates of Bcrp1/BCRP and to investigate the possible role of this transporter in the in vivo pharmacokinetic profile of these compounds and their Secretion into the Milk. Using polarized cell lines, we found that ciprofloxacin, ofloxacin, and norfloxacin are transported by mouse Bcrp1 and human BCRP. In vivo pharmacokinetic studies showed that the ciprofloxacin plasma concentration was more than 2-fold increased in Bcrp1 –/– compared with wild-type mice (1.77 ± 0.73 versus 0.85 ± 0.39 μg/ml, p –/– mice was 1.5-fold higher than that in wild-type mice (48.63 ± 5.66 versus 33.10 ± 4.68 min · μg/ml, p –/– lactating mice. We conclude that Bcrp1 is one of the determinants for the bioavailability of fluoroquinolones and their Secretion into the Milk.
Alfred H. Schinkel - One of the best experts on this subject based on the ideXlab platform.
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multidrug transporter abcg2 breast cancer resistance protein secretes riboflavin vitamin b2 into Milk
Molecular and Cellular Biology, 2007Co-Authors: Antonius E Van Herwaarden, Gracia Merino, Johan W Jonker, Els Wagenaar, Hilde Rosing, Jos H Beijnen, Alfred H. SchinkelAbstract:The multidrug transporter breast cancer resistance protein (BCRP/ABCG2) is strongly induced in the mammary gland during pregnancy and lactation. We here demonstrate that BCRP is responsible for pumping riboflavin (vitamin B2) into Milk, thus supplying the young with this important nutrient. In Bcrp1−/− mice, Milk Secretion of riboflavin was reduced >60-fold compared to that in wild-type mice. Yet, under laboratory conditions, Bcrp1−/− pups showed no riboflavin deficiency due to concomitant Milk Secretion of its cofactor flavin adenine dinucleotide, which was not affected. Thus, two independent Secretion mechanisms supply vitamin B2 equivalents to Milk. BCRP is the first active riboflavin efflux transporter identified in mammals and the first transporter shown to concentrate a vitamin into Milk. BCRP activity elsewhere in the body protects against xenotoxins by reducing their absorption and mediating their excretion. Indeed, Bcrp1 activity increased excretion of riboflavin into the intestine and decreased its systemic availability in adult mice. Surprisingly, the paradoxical dual utilization of BCRP as a xenotoxin and a riboflavin pump is evolutionarily conserved among mammals as diverse as mice and humans. This study establishes the principle that an ABC transporter can transport a vitamin into Milk and raises the possibility that other vitamins and nutrients are likewise secreted into Milk by ABC transporters.
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breast cancer resistance protein bcrp abcg2 transports fluoroquinolone antibiotics and affects their oral availability pharmacokinetics and Milk Secretion
Drug Metabolism and Disposition, 2006Co-Authors: Gracia Merino, Ana I. Alvarez, Mivis M. Pulido, Antonio J. Molina, Alfred H. Schinkel, Julio G. PrietoAbstract:The breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette drug efflux transporter that extrudes xenotoxins from cells in intestine, liver, mammary gland, and other organs, affecting the pharmacological and toxicological behavior of many compounds, including their Secretion into the Milk. The purpose of this study was to determine whether three widely used fluoroquinolone antibiotics (ciprofloxacin, ofloxacin, and norfloxacin) are substrates of Bcrp1/BCRP and to investigate the possible role of this transporter in the in vivo pharmacokinetic profile of these compounds and their Secretion into the Milk. Using polarized cell lines, we found that ciprofloxacin, ofloxacin, and norfloxacin are transported by mouse Bcrp1 and human BCRP. In vivo pharmacokinetic studies showed that the ciprofloxacin plasma concentration was more than 2-fold increased in Bcrp1 –/– compared with wild-type mice (1.77 ± 0.73 versus 0.85 ± 0.39 μg/ml, p –/– mice was 1.5-fold higher than that in wild-type mice (48.63 ± 5.66 versus 33.10 ± 4.68 min · μg/ml, p –/– lactating mice. We conclude that Bcrp1 is one of the determinants for the bioavailability of fluoroquinolones and their Secretion into the Milk.
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the breast cancer resistance protein bcrp abcg2 affects pharmacokinetics hepatobiliary excretion and Milk Secretion of the antibiotic nitrofurantoin
Molecular Pharmacology, 2005Co-Authors: Gracia Merino, Johan W Jonker, Els Wagenaar, Antonius E Van Herwaarden, Alfred H. SchinkelAbstract:Nitrofurantoin is a commonly used urinary tract antibiotic prescribed to lactating woman. It is actively transported into human and rat Milk by an unknown mechanism. Our group has demonstrated an important role of the breast cancer resistance protein (BCRP/ABCG2) in the Secretion of xenotoxins into the Milk. This ATP-binding cassette drug efflux transporter extrudes xenotoxins from cells in intestine, liver, mammary gland, and other organs, affecting the pharmacological and toxicological behavior of many compounds. We investigated whether Bcrp1 is involved in the pharmacokinetic profile of nitrofurantoin and its active Secretion into the Milk. Using polarized cell lines, we found that nitrofurantoin is efficiently transported by murine Bcrp1 and human BCRP. After oral administration of 10 mg/kg nitrofurantoin, the area under the plasma concentrationtime curve in Bcrp1 knockout mice was almost 4-fold higher than in wild-type mice (148.8 ± 30.4 versus 37.5 ± 6.8 min · μg/ml); and after i.v. administration (5 mg/kg), 2-fold higher (139.2 ± 22.0 versus 73.9 ± 9.0 min · μg/ml). Hepatobiliary excretion of nitrofurantoin was almost abolished in Bcrp1 knockout mice (9.6 ± 3.2 versus 0.2 ± 0.1% in wild-type and Bcrp1 knockout mice, respectively). The Milk-to-plasma ratio of nitrofurantoin was almost 80 times higher in wild-type compared with Bcrp1 knockout lactating female mice (45.7 ± 16.2 versus 0.6 ± 0.1). Nitrofurantoin elimination via Milk was quantitatively even higher than hepatobiliary elimination. We conclude that Bcrp1 is an important determinant for the bioavailability of nitrofurantoin and the main mechanism involved in its hepatobiliary excretion and Secretion into the Milk.
Leonardo Murgiano - One of the best experts on this subject based on the ideXlab platform.
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comparison of Milk fat globule membrane mfgm proteins in Milk samples of chianina and holstein cattle breeds across three lactation phases through 2d ief sds page a preliminary study
Food Research International, 2013Co-Authors: Leonardo Murgiano, A. Valentini, Lello Zolla, Angelo Dalessandro, Lorraine ParisetAbstract:Abstract Background Characterisation and identification of proteins involved in Milk production are important to understand the biology of lactation and to manage dairy cattle selection. Many studies have investigated mammary function, Milk Secretion and mammary gland involution, but the critical molecular mechanisms implicated are still incomplete. We focused on Milk Fat Globule Membranes (MFGM), a unique subcategory of proteins mainly originating from the Golgi apparatus and endoplasmic reticulum of mammary gland cells. Methods Using a proteomic approach, 2D-IEF SDS PAGE and ESI MS/MS we compared Milk MFGM belonging to Chianina and Holstein cattle breeds, representative of selection for meat and Milk traits, respectively. Results The two breeds showed different trends in the amount of structural proteins and proteins related to lipid droplet formation, as well as in immunity-related molecules, MFG Secretion, mammary gland epithelium apoptosis and mammary gland involution. Conclusions We successfully isolated the major MFGM proteins and monitored their differences between the two breeds, among three different lactation phases and within the same breed across the lactation phases. The detected differences were relative to the amount of proteins involved in lipid deposition into the droplets, immune system and mammary gland cell apoptosis.
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comparison of Milk fat globule membrane mfgm proteins of chianina and holstein cattle breed Milk samples through proteomics methods
Nutrients, 2009Co-Authors: Leonardo Murgiano, Silvia Bongiorni, A. Valentini, Lello Zolla, Anna Maria Timperio, Lorraine ParisetAbstract:Identification of proteins involved in Milk production is important to understand the biology of lactation. Many studies have advanced the understanding of mammary function and Milk Secretion, but the critical molecular mechanisms implicated in Milk fat Secretion is still incomplete. Milk Fat Globules are secreted from the apical surface of the mammary cells, surrounded by a thin membrane bilayer, the Milk Fat Globule Membrane (MFGM), formed by proteins which have been suggested to be cholesterolemia-lowering factors, inhibitors of cancer cell growth, vitamin binders, bactericidal, suppressors of multiple sclerosis. Using a proteomic approach, we compared MFGM from Milk samples of individuals belonging to two different cattle breeds, Chianina and Holstein, representative of selection for Milk and meat traits, respectively. We were able to isolate some of the major MFGM proteins in the examined samples and to identify differences between the protein fractions of the two breeds. We detected differences in the amount of proteins linked to mammary gland development and lipid droplets formation, as well as host defence mechanisms. We have shown that proteomics is a suitable, unbiased method for the study of Milk fractions proteins and a powerful tool in nutritional genomics.
Lello Zolla - One of the best experts on this subject based on the ideXlab platform.
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comparison of Milk fat globule membrane mfgm proteins in Milk samples of chianina and holstein cattle breeds across three lactation phases through 2d ief sds page a preliminary study
Food Research International, 2013Co-Authors: Leonardo Murgiano, A. Valentini, Lello Zolla, Angelo Dalessandro, Lorraine ParisetAbstract:Abstract Background Characterisation and identification of proteins involved in Milk production are important to understand the biology of lactation and to manage dairy cattle selection. Many studies have investigated mammary function, Milk Secretion and mammary gland involution, but the critical molecular mechanisms implicated are still incomplete. We focused on Milk Fat Globule Membranes (MFGM), a unique subcategory of proteins mainly originating from the Golgi apparatus and endoplasmic reticulum of mammary gland cells. Methods Using a proteomic approach, 2D-IEF SDS PAGE and ESI MS/MS we compared Milk MFGM belonging to Chianina and Holstein cattle breeds, representative of selection for meat and Milk traits, respectively. Results The two breeds showed different trends in the amount of structural proteins and proteins related to lipid droplet formation, as well as in immunity-related molecules, MFG Secretion, mammary gland epithelium apoptosis and mammary gland involution. Conclusions We successfully isolated the major MFGM proteins and monitored their differences between the two breeds, among three different lactation phases and within the same breed across the lactation phases. The detected differences were relative to the amount of proteins involved in lipid deposition into the droplets, immune system and mammary gland cell apoptosis.
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comparison of Milk fat globule membrane mfgm proteins of chianina and holstein cattle breed Milk samples through proteomics methods
Nutrients, 2009Co-Authors: Leonardo Murgiano, Silvia Bongiorni, A. Valentini, Lello Zolla, Anna Maria Timperio, Lorraine ParisetAbstract:Identification of proteins involved in Milk production is important to understand the biology of lactation. Many studies have advanced the understanding of mammary function and Milk Secretion, but the critical molecular mechanisms implicated in Milk fat Secretion is still incomplete. Milk Fat Globules are secreted from the apical surface of the mammary cells, surrounded by a thin membrane bilayer, the Milk Fat Globule Membrane (MFGM), formed by proteins which have been suggested to be cholesterolemia-lowering factors, inhibitors of cancer cell growth, vitamin binders, bactericidal, suppressors of multiple sclerosis. Using a proteomic approach, we compared MFGM from Milk samples of individuals belonging to two different cattle breeds, Chianina and Holstein, representative of selection for Milk and meat traits, respectively. We were able to isolate some of the major MFGM proteins in the examined samples and to identify differences between the protein fractions of the two breeds. We detected differences in the amount of proteins linked to mammary gland development and lipid droplets formation, as well as host defence mechanisms. We have shown that proteomics is a suitable, unbiased method for the study of Milk fractions proteins and a powerful tool in nutritional genomics.