Direct evidence of the generation in human stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin

Kuwata, Hidefumi; Yip, Tai‐Tung; Tomita, Mamoru; Hutchens, T. William

doi:10.1016/s0167-4838(98)00224-6

Cited by 147 publications

(101 citation statements)

References 31 publications

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“…Most of these activities reside in the N-domain of lactoferrin [31]. This domain is also termed as antimicrobial domain due to release of lactoferricin, a more potent antimicrobial peptide, by pepsin digestion [6,32] and lactoferrampin, a second stretch of N1 domains reported as another novel antmicrobial peptide [33]. Therefore, bifidobacteria may make protection against antimicrobial activity of lactoferrin by binding with this domain.…”

Section: Resultsmentioning

confidence: 99%

Bovine lactoferrin region responsible for binding to bifidobacterial cell surface proteins

et al. 2009

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Bovine lactoferrin (bLf) is a multifunctional iron-binding glycoprotein secreted mainly in milk and other secretory fluids. Bovine lactoferrin is reported to promote the growth of bifidobacteria and binding of bLf to bifidobacteria cell is thought to be involved. After separation of bLf half molecule and extraction of surface proteins from bifidobacteria, binding profiles were observed by immunoblotting. No binding was appeared when bLf C-lobe was being reacted with cell surface proteins on PVDF membrane. Conversely, a 50-kDa band was appeared when reacted with either intact bLf or nicked bLf. This result strongly suggests that binding region could be N-lobe.Moreover, blot, probed with nicked bLf, reacted with anti-lactoferricin antibody also produced a 50-kDa band that indicates the binding occurred at lactoferricin region of bLf molecule. Interestingly, despite absence of binding, bLf C-lobe can stimulate the growth of bifidobacteria.

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Section: Resultsmentioning

confidence: 99%

Bovine lactoferrin region responsible for binding to bifidobacterial cell surface proteins

et al. 2009

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“…In addition, it has been demonstrated that lactoferrin, a protein that binds iron in milk, has antimicrobial activity after cleavage (73). However, why an mRNA encoding the antimicrobial peptide hepcidin is induced during iron overload remains an open question.…”

Section: Discussionmentioning

confidence: 99%

A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload

Pigeon

Ilyin

Courselaud

et al. 2001

Journal of Biological Chemistry

1,506

1,264

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Considering that the development of hepatic lesions related to iron overload diseases might be a result of abnormally expressed hepatic genes, we searched for new genes up-regulated under the condition of iron excess. By suppressive subtractive hybridization performed between livers from carbonyl iron-overloaded and control mice, we isolated a 225-base pair cDNA. By Northern blot analysis, the corresponding mRNA was confirmed to be overexpressed in livers of experimentally (carbonyl iron and iron-dextran-treated mice) and spontaneously (␤ 2 -microglobulin knockout mice) ironoverloaded mice. In addition, ␤ 2 -microglobulin knockout mice fed with a low iron content diet exhibited a decrease of hepatic mRNA expression. The murine fulllength cDNA was isolated and was found to encode an 83-amino acid protein presenting a strong homology in its C-terminal region to the human antimicrobial peptide hepcidin. In addition, we cloned the corresponding rat and human orthologue cDNAs. Both mouse and human genes named HEPC are constituted of 3 exons and 2 introns and are located on chromosome 7 and 19, respectively, in close proximity to USF2 gene. In mouse and human, HEPC mRNA was predominantly expressed in the liver. During both in vivo and in vitro studies, HEPC mRNA expression was enhanced in mouse hepatocytes under the effect of lipopolysaccharide. Finally, to analyze the intracellular localization of the predicted protein, we used the green fluorescent protein chimera expression vectors. The murine green fluorescent protein-prohepcidin protein was exclusively localized in the nucleus. When the putative nuclear localization signal was deleted, the resulting protein was addressed to the cytoplasm. Taken together, our data strongly suggest that the product of the new liver-specific gene HEPC might play a specific role during iron overload and exhibit additional functions distinct from its antimicrobial activity.

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“…37,38 Although a recent study failed to demonstrate the presence of dietary bovine lactoferrin or functional fragments of bovine lactoferrin such as LfcinB in the portal blood of rats, 39 the systemic antiangiogenic activity of ingested bovine lactoferrin in both rats and mice 35,36 suggests that transfer of LfcinB to circulating blood is likely to in fact take place. However, it is important to realize that a systemic distribution of LfcinB at the concentration (200 g/ml) that showed antiangiogenic activity in our in vivo and in vitro assays cannot be attained by the normal consumption of dairy products containing bovine lactoferrin as a source of LfcinB because cow's milk, for example, contains less than 100 mg/L lactoferrin.…”

Section: Discussionmentioning

confidence: 99%

Bovine Lactoferricin Inhibits Basic Fibroblast Growth Factor- and Vascular Endothelial Growth Factor165-Induced Angiogenesis by Competing for Heparin-Like Binding Sites on Endothelial Cells

Mader

Smyth

Marshall

et al. 2006

The American Journal of Pathology

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Direct evidence of the generation in human stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin

Cited by 147 publications

References 31 publications

Bovine lactoferrin region responsible for binding to bifidobacterial cell surface proteins

Bovine lactoferrin region responsible for binding to bifidobacterial cell surface proteins

A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload

Bovine Lactoferricin Inhibits Basic Fibroblast Growth Factor- and Vascular Endothelial Growth Factor165-Induced Angiogenesis by Competing for Heparin-Like Binding Sites on Endothelial Cells

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