Utilization of dipeptides by the caprine mammary gland for milk protein synthesis

1994 ◽  
Vol 267 (1) ◽  
pp. R1-R6 ◽  
Author(s):  
F. R. Backwell ◽  
B. J. Bequette ◽  
D. Wilson ◽  
A. G. Calder ◽  
J. A. Metcalf ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mammary Gland ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Milk Protein ◽  
Common Mechanism ◽  
Dairy Goats ◽  
Peptide Hydrolysis ◽  
Lactating Mammary Gland

Specific use by the mammary gland in vivo of amino acids (AA) of peptide origin has been demonstrated in lactating dairy goats using a dual-labeled tracer technique involving close-arterial (external pudic artery, EPA) infusion of 13C-labeled dipeptides. The extent of utilization does not appear to differ for glycyl-L-[1-13C]phenylalanine and glycyl-L-[1-13C]leucine, perhaps indicative of a common mechanism by which AA are incorporated from peptide into milk protein. [1-13C]phenyl-alanine of peptide origin appears to be concentrated within the red blood cell, suggesting a role for the erythrocyte in peptide metabolism in vivo. In conclusion, it appears that the lactating mammary gland of goats has the ability to utilize AA of peptide origin for milk protein synthesis, and while the mechanism by which [1-13C]AA are incorporated into milk protein is not clear, it may involve peptide hydrolysis by either mammary cell surface or red blood cell hydrolases followed by uptake of liberated AA by the mammary gland.

Evidence for the utilization of peptides for milk protein synthesis in the lactating dairy goat in vivo

1996 ◽  
Vol 271 (4) ◽  
pp. R955-R960 ◽  
Author(s):  
F. R. Backwell ◽  
B. J. Bequette ◽  
D. Wilson ◽  
J. A. Metcalf ◽  
M. F. Franklin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Mammary Gland ◽  
Milk Protein ◽  
Indirect Evidence ◽  
Dairy Goat ◽  
Dairy Goats ◽  
Milk Casein ◽  
Amino Acid Precursors

Precursors for milk protein synthesis have been examined in lactating dairy goats using arteriovenous difference and isotope kinetic techniques. Certain amino acids, such as phenylalanine and histidine, are taken up by the mammary gland in quantities that are insufficient to account for their output in milk protein. Some amino acids have been shown to be present in significant quantities (10-30% of total non-protein-bound amino acids) as peptides (< 1,500 Da) in the arterial supply to the mammary gland, although methodological considerations make it difficult to accurately assess the extent of their uptake across the tissue bed. Indirect evidence for the utilization of peptides for milk protein synthesis in vivo has been obtained, however, by examination of the kinetics of milk casein labeling during long-term (24 h) systemic infusion of [1-13C]phenylalanine and [1-13C]leucine. Comparison of plateau enrichments for blood, plasma, and casein indicate that, although, for leucine, the plasma free pool seems to provide all the leucine for milk protein synthesis, sources other than the labeled plasma free amino acids contribute phenylalanine (10-20%) for casein biosynthesis. These findings raise questions relating to the type and source of amino acid precursors used by tissues for protein synthesis.

Effect of intravenous histidine or histidine peptide infusion on milk protein yield in lactating goats with an induced histidine deficiency

1996 ◽  
Vol 1996 ◽  
pp. 180-180
Author(s):  
F.R.C. Backwell ◽  
B.J. Bequette ◽  
L.A. Crompton ◽  
C.K. Reynolds ◽  
D.E. Beever ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mammary Gland ◽  
Stable Isotope ◽  
Milk Production ◽  
Present Experiment ◽  
Milk Protein ◽  
Jugular Vein ◽  
Dairy Goats ◽  
Lactating Goats

Studies involving infusion of stable isotope labelled peptides have shown that the mammary gland has the ability to utilise peptide-derived AA for milk protein synthesis (Backwell et al., 1994a) and that peptides may be involved in the supply of phenylalanine to the mammary gland in vivo (Backwell et al., 1994b). The aim of the present experiment was to compare milk production responses to systemic (jugular vein) provision of histidine as free AA or as a peptide (glycyl-histidine) in lactating dairy goats with an induced histidine deficiency.

Effect of intravenous histidine or histidine peptide infusion on milk protein yield in lactating goats with an induced histidine deficiency

1996 ◽  
Vol 1996 ◽  
pp. 180-180
Author(s):  
F.R.C. Backwell ◽  
B.J. Bequette ◽  
L.A. Crompton ◽  
C.K. Reynolds ◽  
D.E. Beever ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mammary Gland ◽  
Stable Isotope ◽  
Milk Production ◽  
Present Experiment ◽  
Milk Protein ◽  
Jugular Vein ◽  
Dairy Goats ◽  
Lactating Goats

Studies involving infusion of stable isotope labelled peptides have shown that the mammary gland has the ability to utilise peptide-derived AA for milk protein synthesis (Backwell et al., 1994a) and that peptides may be involved in the supply of phenylalanine to the mammary gland in vivo (Backwell et al., 1994b). The aim of the present experiment was to compare milk production responses to systemic (jugular vein) provision of histidine as free AA or as a peptide (glycyl-histidine) in lactating dairy goats with an induced histidine deficiency.

Peptide utilisation by the mammary gland of lactating goats.

1994 ◽  
Vol 1994 ◽  
pp. 26-26
Author(s):  
F.R.C. Backwellf ◽  
B J. Bequettet ◽  
J.A. Metcalf ◽  
D. Wray-Cahen ◽  
L. Crompton ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Dairy Cows ◽  
Milk Protein ◽  
Dairy Goats ◽  
Small Peptides ◽  
Lactating Goats ◽  
Uptake Studies ◽  
Milk Casein ◽  
Casein Synthesis

During lactation the ruminant mammary gland removes relatively large quantities of circulating amino acids (AA) to meet the requirements for milk protein synthesis but arterio-venous uptake studies in dairy cows (1) have indicated that the uptake of certain AA may be insufficient to account for their output as milk protein. The apparent deficit may be accounted for by the use of AA supplied to the gland as small peptides or proteins. A dual-labelled tracer approach involving infusion of [13C]-labelled peptides into the external pudic artery which supplies blood directly to the mammary gland demonstrated that dipeptide-bound AA can be utilised as direct precursors for milk casein synthesis in lactating dairy goats (2). However, previous studies using vascular infusion of [13C]-labelled free AA (3) have provided equivocal data on involvement of non-labelled extra-mammary derived peptides/proteinsin vivoin the biosynthesis of milk protein.

Milk Protein Precursors in the Goat During Late Lactation

1993 ◽  
Vol 1993 ◽  
pp. 1-1
Author(s):  
B.J. Bequette ◽  
F.R.C. Backwell ◽  
A.G. Calder ◽  
J.A. Metcalf ◽  
D. Wray-Cahen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Mammary Gland ◽  
Milk Protein ◽  
Protein S ◽  
Dairy Goats ◽  
Protein Precursor ◽  
Previous Hypothesis ◽  
Casein Protein ◽  
Isotope Kinetics

Previously, we have reported on work in dairy goats using stable isotope kinetics to examine the precursors for milk protein synthesis (1). Contrary to a previous hypothesis (2), these results suggested that blood free amino acids (AA) are not simply transported into the mammary gland and incorporated directly into milk protein. Although the latter may still occur, a substantial amount of the AA for milk protein synthesis appears to be channelled through constitutive mammary gland protein(s) first. Moreover, the data indicated that a proportion (12-20%) of the casein protein precursor may be derived from extra-mammary sources other than blood free AA, e.g. peptides and/or proteins. It may be possible therefore to alter milk protein synthesis by the provision of different forms of precursor amino acids. Since the previous study was in goats during early lactation (day 61 ± 11), the present study reports on the precursors for milk protein synthesis in goats during late lactation, and allows a comparison between stages of lactation.

scholarly journals Effects of High-Grain Diet with Buffering Agent on the Milk Protein Synthesis in Lactating Goats

2020 ◽  
Author(s):  
Meilin He ◽  
Xintian Nie ◽  
Huanhuan Wang ◽  
Shuping Yan ◽  
Yuanshu Zhang
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Mammary Gland ◽  
Amino Acid ◽  
Western Blot ◽  
Milk Protein ◽  
Mtor Pathway ◽  
Production Performance ◽  
Dairy Goats ◽  
Buffering Agent

AbstractFeeding of straw as main roughage with numerous high-grain diets improves the performance of ruminants but it can easily lead to subacute ruminal acidosis. In recent years, buffering agent is applied to prevent the acid poisoning of ruminants and improve the production performance of ruminants in animal husbandry. it is necessary to understand feeding high-grain diet with buffering agent which transport carriers amino acids mainly take amino acids into the mammary gland and the signal mechanism of amino acids in the mammary gland synthesize milk proteins. To gain insight on the effects of a high-grain diet with buffering agent on the amino acids in the jugular blood, and the effects of amino acids on the synthesis of milk protein, commercial kit and high performance liquid chromatography (HPLC) were applied to determine the concentration of amino acids of jugular blood samples, quantitative real-time PCR, comparative proteomic approach and western blot were employed to investigate proteins differentially expressed in mammary tissues and the mechanism of amino acids on the synthesis of milk protein in mammary gland of lactating dairy goats fed high-grain diet with buffering agent or only high-grain diet.Results showed that feeding high-grain diet with buffering agent to lactating dairy goats could outstanding increase amino acid content of jugular blood (p<0.05), and mRNA transcriptional level of amino acid transporters in the mammary gland were also increased; the CSN2 and LF protein expression level were significant higher by 2-DE technique, MALDI-TOF/TOF proteomics analyzer and western blot analysis further validated in mammary of lactating dairy goats compared with high-grain group; the research on the mechanism of milk protein synthesis increasing suggested that it was related to the activation of mTOR pathway signaling.Feeding of high-grain diet with buffering agent promoted the jugular vein blood of amino acids concentration, and more amino acids flowed into the mammary. In addition, milk protein synthesis was increased and the increase of milk protein synthesis was related to the activation of mTOR pathway signalling.

Effects of Preloading of Stannous Compounds on the Distribution of 99mTc-Pertechnetate

1977 ◽  
Vol 16 (01) ◽  
pp. 26-29 ◽  
Author(s):  
D. D. Greenberg ◽  
P. Som ◽  
G. E. Meinken ◽  
D. F. Sacker ◽  
H. L. Atkins ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Plasma Ratio ◽  
99Mtc Pertechnetate ◽  
Time Period ◽  
Stannous Ion ◽  
Distribution Studies

Summary 99mTc-pertechnetate distribution studies were performed in rabbits and mice following pretreatment between 5—336 hours with various routinely used stannous complexes (HSA, MAA, GHT, DTPA, PYPs) containing different amounts of Sn++ (0.17 —15.0 μ mg/kg). Beyond a concentration of 0.26 mg/kg of Sn++ an alteration in 99mTc-pertechnetate distribution was observed. The red blood cell was found to be the most prominent target. An in-vivo reduction of 99mTc-pertechnetate apparently occurred by the presence of stannous ion within the red blood cell. Preloading time period between 5—24 hours did not alter the uptake of RBC/plasma ratio. Beyond that period it decreased slowly and still persisted up to 2 weeks following pretreatment. RBC/ plasma ratio of 99mTcO4 - increased with increased Sn++ content of various commercially available pharmaceutical kits.

scholarly journals Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15

2021 ◽  
Author(s):  
Shannon L. McArdel ◽  
Anne-Sophie Dugast ◽  
Maegan E. Hoover ◽  
Arjun Bollampalli ◽  
Enping Hong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Blood Cell ◽  
Nk Cells ◽  
Red Blood Cell ◽  
Safety Profile ◽  
Nk Cell ◽  
Cell Activity ◽  
In Vivo Studies

AbstractRecombinant agonists that activate co-stimulatory and cytokine receptors have shown limited clinical anticancer utility, potentially due to narrow therapeutic windows, the need for coordinated activation of co-stimulatory and cytokine pathways and the failure of agonistic antibodies to recapitulate signaling by endogenous ligands. RTX-240 is a genetically engineered red blood cell expressing 4-1BBL and IL-15/IL-15Rα fusion (IL-15TP). RTX-240 is designed to potently and simultaneously stimulate the 4-1BB and IL-15 pathways, thereby activating and expanding T cells and NK cells, while potentially offering an improved safety profile through restricted biodistribution. We assessed the ability of RTX-240 to expand and activate T cells and NK cells and evaluated the in vivo efficacy, pharmacodynamics and tolerability using murine models. Treatment of PBMCs with RTX-240 induced T cell and NK cell activation and proliferation. In vivo studies using mRBC-240, a mouse surrogate for RTX-240, revealed biodistribution predominantly to the red pulp of the spleen, leading to CD8 + T cell and NK cell expansion. mRBC-240 was efficacious in a B16-F10 melanoma model and led to increased NK cell infiltration into the lungs. mRBC-240 significantly inhibited CT26 tumor growth, in association with an increase in tumor-infiltrating proliferating and cytotoxic CD8 + T cells. mRBC-240 was tolerated and showed no evidence of hepatic injury at the highest feasible dose, compared with a 4-1BB agonistic antibody. RTX-240 promotes T cell and NK cell activity in preclinical models and shows efficacy and an improved safety profile. Based on these data, RTX-240 is now being evaluated in a clinical trial.

scholarly journals Absence of the Adaptor Protein PEA-15 Is Associated with Altered Pattern of Th Cytokines Production by Activated CD4+ T Lymphocytes In Vitro, and Defective Red Blood Cell Alloimmune Response In Vivo

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0136885 ◽  
Author(s):  
Stéphane Kerbrat ◽  
Benoit Vingert ◽  
Marie-Pierre Junier ◽  
Flavia Castellano ◽  
François Renault-Mihara ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Adaptor Protein
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