Identification and partial characterization of multiple forms of biologically active EGF in rat milk

Schaudies, R. P.; Grimes, J.; Wray, H. Linton; Koldovský, Otakar

doi:10.1152/ajpgi.1990.259.6.g1056

Cited by 23 publications

(24 citation statements)

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“…EGF is one of several growth factors found in breast milk, which was first characterized over three decades ago (Schaudies et al 1990). EGF is a peptide with significant interspecific structural homology (Marti et al 1989), and milk EGF is both sourced from maternal circulation and synthesized locally in mammary tissue.…”

Section: Adiponectinmentioning

confidence: 99%

Mount Pinatubo, Inflammatory Cytokines, and the Immunological Ecology of Aeta Hunter-Gatherers

Bernstein

Dominy

2013

Human Biology

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Early growth cessation and reproduction are predicted to maximize fitness under conditions of high adult mortality, factors that could explain the pygmy phenotype of many rainforest hunter-gatherers. This lifehistory hypothesis is elegant but contentious in part because it lacks a clear biological mechanism. One mechanism stems from the field of human immunological ecology and the concept of inflammation "memory" across the life cycle and into subsequent generations. Maternal exposures to disease can infl uence immunological cues present in breast milk; because maternal provisioning via lactation occurs during critical periods of development, it is plausible that these cues can also mediate early growth cessation and small body size. Such epigenetic hypotheses are difficult to test, but the concept of developmental programming is attractive because it could explain how the stature of a population can change over time, in terms of both secular increases and rapid intergenerational decreases. Here we explore this concept by focusing on the Aeta, a population of former hunter-gatherers, and the Ilocano, a population of rice farmers. We predicted that Aeta mothers would produce breast milk with higher concentrations of four bioactive factors due to high infectious burdens. Further, we predicted that the concentrations of these factors would be highest in the cohort of women born in the early 1990s, when exposure to infectious disease was acute following the eruption of Mount Pinatubo in June 1991. We analyzed levels of adiponectin, C-reactive protein, and epidermal growth factor in the milk of 24 Aeta and 31 Ilocano women and found no detectable differences, whereas levels of transforming growth factor-β 2 were elevated among the Aeta, particularly as a function of maternal age. We found no difference between cohorts divided by the volcanic eruption (n = 43 born before, n = 12 born after). We discuss the implications of our findings for the terminal investment hypothesis and we suggest that the historical ecology of the Aeta is a promising model system for testing epigenetic hypotheses focused on the evolution of small body size. Abstract Early growth cessation and reproduction are predicted to maximize fitness under conditions of high adult mortality, factors that could explain the pygmy phenotype of many rainforest hunter-gatherers. This life-history hypothesis is elegant but contentious in part because it lacks a clear biological mechanism. One mechanism stems from the field of human immunological ecology and the concept of inflammation "memory" across the life cycle and into subsequent generations. Maternal exposures to disease can infl uence immunological cues present in breast milk; because maternal provisioning via lactation occurs during critical periods of development, it is plausible that these cues can also mediate early growth cessation and small body size. Such epigenetic hypotheses are difficult to test, but the concept of developmental programming is attractive because it could explain how the...

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Section: Adiponectinmentioning

confidence: 99%

Mount Pinatubo, Inflammatory Cytokines, and the Immunological Ecology of Aeta Hunter-Gatherers

Bernstein

Dominy

2013

Human Biology

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“…The presence of EGF-containing peptides of varying molecular masses (from 6 to 160 kDa) in urine (37,42,43) and milk (22) of different species indicates that EGF can be released (shed) from its membrane-anchored precursor. This occurs through proteolytic cleavage in the juxtamembrane region.…”

Section: Epidermal Growth Factor (Egf)mentioning

confidence: 99%

“…In order to lead to the ultimate, mature 6-kDa form of the molecule, the ectodomain needs to be further maturated in the extracellular medium. It has already been shown that, in vitro, mature EGF could be released from its precursor through the action of different type of proteases; acidic protease such as pepsin (36) or serine-proteases such as trypsin (22,39,41) and plasmin (44). Moreover, membrane fractions of both kidney (45,46) and mammary gland (47) contain a membrane-bound proteolytic activity that colocalized with pro-EGF and released soluble EGF from its membraneassociated precursor.…”

Section: Epidermal Growth Factor (Egf)mentioning

confidence: 99%

Regulated Cell Surface Pro-EGF Ectodomain Shedding Is a Zinc Metalloprotease-dependent Process

Gall

Auger

Dreux

et al. 2003

Journal of Biological Chemistry

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Epidermal growth factor receptor (EGFR) ligands are synthesized as type I membrane protein precursors exposed at the cell surface. Shedding of the ectodomain of these proteins is the way cells regulate the equilibrium between cell-associated and diffusible forms of these growth factors. Whereas the regulated shedding of transforming growth factor-␣, HB-EGF, and amphiregulin precursors have been clearly established, regulation of full-length pro-EGF shedding has not been clearly demonstrated. Here, using both wild-type and M2 mutant CHO-K1 as well as HeLa cell lines transiently transfected with epitope-tagged rat pro-EGF expression plasmid, we demonstrate that these cells synthesize EGF as a high molecular weight membrane-associated precursor glycoprotein expressed at the cell surface. All cell lines are able to release the entire ectodomain of pro-EGF in the extracellular medium following juxtamembrane cleavage of the precursor once it is present at the cell surface. More significantly we clearly established that CHO-M2 and HeLa cells only constitutively release low levels of pro-EGF. This shedding is a regulated phenomenon in wild-type CHO cells where it can be induced by different agents such as phorbol 12-myristate 13-acetate (PMA), pervanadate, and serum but not by calcium ionophores. Using specific inhibitors as well as protein kinase C (PKC) depletion, PMA stimulation was shown to be completely dependent on PKC activation whereas pervanadate and serum stimulation were not. Regulated ectodomain shedding involves the activity of a zinc metalloprotease as determined by inhibition with phenantrolin and TAPI-2 and by the results obtained with the CHO-M2 shedding defective mutant cell line. Comparison of the ability of CHO and HeLa cell lines to shed pro-EGF and pro-TNF-␣ upon stimulation greatly suggests that TACE (ADAM 17) may not be the ectoprotease involved in the secretion of pro-EGF ectodomain and that this protease, which remains to be identified, shows a restricted cellular expression pattern.

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“…EGF concentrations in milk and stomach contents were measured by a modification of a radioimmunoassay published previously [38]. Anti-rat EGF antibody, purified rat EGF, and goat anti-rabbit IgG were purchased from Biomedical Technologies (Stoughton, MA).…”

Section: Egf Assaymentioning

confidence: 99%

Epidermal Growth Factor and Parathyroid Hormone-related Peptide mRNA in the Mammary Gland and their Concentrations in Milk: Effects of Postpartum Hypoxia in Lactating Rats

Bruder

Hoof

Young³

et al. 2008

Horm Metab Res

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The physiological adaptations of the neonatal rat to hypoxia from birth include changes in gastrointestinal function and intermediary metabolism. We hypothesized that the hypoxic lactating dam would exhibit alterations in mammary gland function leading to changes in the concentration of milk peptides that are important in neonatal gastrointestinal development. The present study assessed the effects of chronic hypoxia on peptides produced by the mammary glands and present in milk. Chronic hypoxia decreased the concentration of epidermal growth factor (EGF) in expressed milk and pup stomach contents and decreased maternal mammary gland Egf mRNA. The concentration of parathyroid hormone-related protein (PTHrp) was unchanged in milk and decreased in pup stomach contents; however, mammary Pthlh mRNA was increased by hypoxia. There was a significant increase in adiponectin concentrations in milk from hypoxic dams. Chronic hypoxia decreased maternal body weight, and pair feeding normoxic dams an amount of food equivalent to hypoxic dam food intake decreased body weight to an equivalent degree. Decreased food intake did not affect the expression of Egf, Pthlh, or Lep mRNA in mammary tissue. The results indicated that chronic hypoxia modulated mammary function independently of hypoxia-induced decreases in maternal food intake. Decreased EGF and increased adiponectin concentrations in milk from hypoxic dams likely affect the development of neonatal intestinal function.

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Identification and partial characterization of multiple forms of biologically active EGF in rat milk

Cited by 23 publications

References 0 publications

Mount Pinatubo, Inflammatory Cytokines, and the Immunological Ecology of Aeta Hunter-Gatherers

Mount Pinatubo, Inflammatory Cytokines, and the Immunological Ecology of Aeta Hunter-Gatherers

Regulated Cell Surface Pro-EGF Ectodomain Shedding Is a Zinc Metalloprotease-dependent Process

Epidermal Growth Factor and Parathyroid Hormone-related Peptide mRNA in the Mammary Gland and their Concentrations in Milk: Effects of Postpartum Hypoxia in Lactating Rats

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