Proteolysis of Milk Fat Globule Membrane Proteins in Preterm Milk: A Transient Phenomenon with a Possible Biological Role?

Abstract

Milk fat globule membrane (MFGM) proteins constitute a milk fraction currently of great interest, as they appear to significantly contribute to milk protective role. We investigated these proteins in human preterm colostrum and milk. For the former we found a peculiar 2-DE pattern, with a spot concentration at low molecular weight, which mass spectrometry analysis showed to be fragments belonging to some MFGM proteins with a well-known biological and especially immunological role: lactadherin, membrane-associated lactoferrin, butyrophilin, clusterin and heavy-chain immunoglobulin. Since we were able to rule out protease activity after specimen collection, we hypothesize the localization of the proteolytic enzymes in the alveolar cell membranes of the mammary gland. This mechanism is probably under hormonal control and the unexpected advent of preterm delivery would not allow hormonal conditions typical of lactation to occur immediately, causing a delay in enzymatic inhibition. This hypothesis is supported by some of our results, picturing a peculiar transient phenomenon of adaptation of the mammary-gland-membrane proteins after preterm delivery. Further studies will be required to verify whether the presence of protein fragments exerts a specific biological and immuno-defensive role in preterm infants, thus adding evidence to the outstanding biological role and benefits of mother's own milk in feeding preterm infants.

Exploring Human Milk Dynamics: Interindividual Variation in Milk Proteome, Peptidome, and Metabolome

“…Clusters 5 and 10 are dominated by peptides from MFGM proteins (median CV of 75.5 and 81.8%, respectively). The clustering of peptides of MFGM proteins is in line with Giuffrida et al, who proposed a specific mechanism for proteolysis of MFGM proteins by proteolytic enzymes in the alveolar cell membranes . This is further supported by the fact that most peptides in these clusters do not match the specificity of plasmin (Figure ).…”

“…The clustering of peptides of MFGM proteins is in line with Giuffrida et al, who proposed a specific mechanism for proteolysis of MFGM proteins by proteolytic enzymes in the alveolar cell membranes. 62 This is further supported by the fact that most peptides in these clusters do not match the specificity of plasmin ( Figure 7 ). As shown in Figure 6 , several clusters dominated by peptides from PIGR or MFGM related proteins (5, 8, 10, and 11) show a strong negative correlation with total peptide intensity.…”

“…This indicates that the degradation of caseins is distinct from the degradation of other proteins, which might be due to their association in micelles. 62 This is further supported by the fact that most peptides in these clusters do not match the specificity of plasmin (Figure 7). As shown in Figure 6, several clusters dominated by peptides from PIGR or MFGM related proteins (5, 8, 10, and 11) show a strong negative correlation with total peptide intensity.…”

In the Short‐term, Milk Fat Globule Epidermal Growth Factor‐8 Causes Site‐specific Intestinal Growth in Resected Piglets

“…Milk fat globule epidermal growth factor-8 (MFG-E8), formerly lactadherin, is one of those major MFG proteins in human milk (6). Importantly, this protein is protected from gastric degradation in preterm infants (5,7). The structure of MFG-E8 has been conserved across many mammalian species, including human and bovine, suggestive of an important role in mammalian development (8).…”