Proteolytic activation of proteose peptone component 3 by release of a C-terminal peptide with antibacterial properties

Pedersen, Lise Refstrup Linnebjerg; Hansted, Jon G.; Nielsen, Søren Achim; Petersen, Torben E.; Sørensen, Uffe B. Skov; Otzen, Daniel E.; Sørensen, Esben S.

doi:10.3168/jds.2011-4837

Cited by 11 publications

(6 citation statements)

References 44 publications

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“…Even though the cause of this antiviral activity has not been well stated yet, there is some evidence that PP3 operates as a precursor protein that, upon proteolysis, releases peptides with antibacterial capacity. 27,34 Effect of Cream Washing on the Neutralizing Activity of Diverse Milk Fractions on Bovine Rotavirus Infectivity. The impact of cream washing on the derived fractions from bovine and ovine milk was also investigated.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Furthermore, an additional Sephadex G-75 gel chromatography step was developed in the presence of urea to separate PP3 fragments of 28 and 17 kDa. Additionally, proteolytic degradation of PP3 was carried out, according to the method of Pedersen et al, 27 by incubating PP3 (8 mg/mL solution) in 0.1 N NH 4 HCO 3 , pH 8, with trypsin (1% w/w) for 2 h at 37 °C, to test the antirotaviral activity of the resulting peptides. Bovine immunoglobulins G (IgG) were isolated, according to the method of Mainer et al, 28 by precipitation with ammonium sulfate followed by DEAE-Sepharose chromatography.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Antirotaviral Activity of Bovine and Ovine Dairy Byproducts

Parrón

Ripollés

Pérez

et al. 2017

J. Agric. Food Chem.

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Rotaviral gastroenteritis is associated with significant morbidity in developed countries and a high rate of infant mortality in developing countries. Diverse studies have demonstrated that a wide range of milk-derived fractions exhibit antirotaviral activity. The present study shows the antirotaviral activity of some bovine and ovine dairy byproducts, buttermilk, butter serum, and milk fat globule membrane (MFGM), and evaluates the effect of cream washing and heat treatment on that activity. Furthermore, the rotavirus-neutralizing activity was evaluated for some MFGM proteins, such as xanthine oxidase and lactophorin. Ovine and bovine buttermilk reached rotavirus-neutralizing values of 51.3 and 32.2%, at 1 mg/mL, respectively. The cream washing process led to a significant decrease in the antirotaviral activity of fractions. This activity was also influenced by heat treatment. Treatment at 75 °C for 20 s caused 24.6 and 36.1% decreases of activity in bovine and ovine buttermilk, respectively, and 85 °C for 10 min caused decreases of 80.9 and 79.0% in both fractions, respectively.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Antirotaviral Activity of Bovine and Ovine Dairy Byproducts

Parrón

Ripollés

Pérez

et al. 2017

J. Agric. Food Chem.

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“…The concentration of plasminogen in bovine milk has been reported to be 0.8 to 2.8 μg/mL, whereas the concentration of plasmin is 0.1 to 0.7 μg/mL (Ozen et al, 2003). Plasmin cleavage of different proteins in milk, such as the caseins and component PP3, has been reported (Sørensen and Petersen, 1993b;Wedholm et al, 2008;Pedersen et al, 2012). Plasmin is an alkaline protease that cleaves substrate proteins on the carboxyl side of lysine and arginine residues with a preference for lysine (Weinstein and Doolittle, 1972).…”

Section: Figure 4 Identified Cleavage Sites In Bovine Milk Osteopontin (Opn) (A)mentioning

confidence: 99%

“…This shows that the N-terminal fragments in bovine milk are competently able to signal and interact with integrins. Proteolytic cleavage of other milk proteins such as, for instance, the caseins, lactoferrin, α-LA, and component PP3 in milk or the gastrointestinal tract has been reported to increase or alter their biological functions (Pedersen et al, 2012;Lönnerdal, 2013). Similarly, the cleavage of bOPN in bovine milk could be an activation step that leads to the formation of highly bioactive fragments, which then can exert bioactive functions such as signaling via integrins in milk and the gastrointestinal tract.…”

Section: Figure 4 Identified Cleavage Sites In Bovine Milk Osteopontin (Opn) (A)mentioning

confidence: 99%

Osteopontin is highly susceptible to cleavage in bovine milk and the proteolytic fragments bind the αVβ3-integrin receptor

Christensen

Sørensen

2014

Journal of Dairy Science

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Site-specific and partial proteolysis of milk proteins can both alter and increase their biological activity. The milk protein osteopontin (OPN) is a highly phosphorylated integrin-binding molecule present in most tissues and body fluids. Osteopontin is a biological substrate for matrix metalloproteinases, thrombin, plasmin, and cathepsin D. These proteases cleave OPN at several positions near the integrin-binding sequence Arg-Gly-Asp(138). This cleavage can either increase or reduce the ability of OPN to bind integrins and illustrates that small differences in the cleavage pattern can have a substantial effect on the functionality of OPN. Bovine milk OPN (bOPN) exists in both intact full-length and cleaved forms, and in this study, 6 N-terminal bOPN fragments originating from proteolytic cleavage were purified and characterized by mass spectrometry. These fragments were generated by cleavage at the Lys(145)-Ser(146), Arg(147)-Ser(148), Lys(149)-Lys(150), Phe(151)-Arg(152), Arg(152)-Arg(153), and Arg(153)-Ser(154) peptide bonds. The principal protease in milk, plasmin, appeared to cleave 3 of these sites. However, the major cleavage site was observed to be at the Phe(151)-Arg(152) bond, which does not match the specificity of plasmin. The bOPN fragments were shown to interact with the integrin receptor αVβ₃ as efficiently as the well-characterized and highly active OPN fragment Ile(1)-Arg(152), generated by thrombin cleavage of human milk OPN. These data show that OPN in milk is highly susceptible to proteolytic cleavage in the region containing the integrin-binding motifs, and the generated fragments are highly capable of binding cells via the αVβ₃-integrin.

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“…RAD51 has been reported to be associated with bovine oocytes meiosis progress [49,50]. Some candidate genes (e.g., LAP3, GLYCAM1, PDE1B, MICALL2, NPC1) are related with other economic traits in cattle such as milk production, carcass traits, body weight, body height, and body length [51][52][53][54][55].…”

Section: Candidate Genomic Regions For the Intercepts And Slopesmentioning

confidence: 99%

Genotype-by-environment Interaction in Holstein Heifer Fertility Traits using Single-step Genomic Reaction Norm Models

Shi

Brito

et al. 2020

Preprint

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Background: The effect of heat stress on livestock production is a worldwide issue, where animal performance is influenced by exposure to high environmental temperatures, indicating the existence of possible genotype-by-environment interactions (G´E). The main objectives of this study were to (1) detect the time periods in which heifer fertility traits are more sensitive to the exposure to high environmental temperature and/or humidity, (2) investigate G´E due to heat stress in heifer fertility traits, and (3) identify genomic regions associated with heifer fertility and heat stress in Holstein cattle. Results: Phenotypic records for three heifer fertility traits (i.e., age at first calving, interval from first to last service, and conception rate at the first service) were collected, from 2005 to 2018, for 56,998 Holstein heifers raised in 15 herds in the Beijing area (China). By integrating environmental data including hourly air temperature and relative humidity, the critical periods in which the heifers are more sensitive to heat stress were defined as <=30 days before the first service for age at first calving and interval from first to last service, or 10 days before and <= 60 days after the first service for conception rate. Using reaction norm models, significant G´E was detected for all three traits regarding both environmental gradients, proportion of days exceeding heat threshold and minimum temperature humidity index. Through single-step genome-wide association study, PLAG1, AMHR2, SP1, KRT8, KRT18, MLH1, and EOMES were suggested as candidate genes for heifer fertility while HCRTR1, AGRP, PC, and GUCY1B1 were for heat tolerance. Conclusions: The critical periods in which reproductive perfromances of heifers are more sensitive to heat stress are trait-dependent. Thus, detailed analysis should be conducted to determine this particular period for other fertility traits. The considerable magnitude of G´E and sire re-ranking indicates the necessity to consider G´E in breeding schemes. This will enable selection of more heat-tolerant animals with high reproductive efficiency under harsh climatic conditions. The candidate genes identified to be linked with response to heat stress provide a better understanding of the underlying biological mechanisms of heat tolerance in dairy cattle.

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Proteolytic activation of proteose peptone component 3 by release of a C-terminal peptide with antibacterial properties

Cited by 11 publications

References 44 publications

Antirotaviral Activity of Bovine and Ovine Dairy Byproducts

Antirotaviral Activity of Bovine and Ovine Dairy Byproducts

Osteopontin is highly susceptible to cleavage in bovine milk and the proteolytic fragments bind the αVβ3-integrin receptor

Genotype-by-environment Interaction in Holstein Heifer Fertility Traits using Single-step Genomic Reaction Norm Models

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