Interaction of Human Lactoferrin with Cell Adhesion Molecules through RGD Motif Elucidated by Lactoferrin-binding Epitopes

Sakamoto, Kotaro; Ito, Yuji; Mori, Toshiyuki; Sugimura, Kazuhisa

doi:10.1074/jbc.m604974200

Cited by 41 publications

(24 citation statements)

References 26 publications

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“…Both the cellular and biochemical signals were decreased when the cells were exposed for 1 hour at 37°C to 10 IU/ml Hep just before termination of the cultures (Fig. 7, A-C), leading us to assume that Lf was bound essentially to HSPGs, as described previously in other systems (Sakamoto et al, 2006). Figure 7D depicts variations in Lf fluorescence intensities in TH 1 neurons from Lftreated cultures exposed or not acutely to Hep.…”

Section: Resultsmentioning

confidence: 92%

The Iron-Binding Protein Lactoferrin Protects Vulnerable Dopamine Neurons from Degeneration by Preserving Mitochondrial Calcium Homeostasis

2013

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Previous studies on postmortem human brain tissue have shown that the iron-binding glycoprotein lactoferrin is upregulated in dopamine (DA) neurons resistant to degeneration in Parkinson disease (PD). To study how this could possibly relate to disease progression, we used midbrain cultures and experimental settings that model the progressive loss of DA neurons in this disorder. Human lactoferrin of either recombinant or natural origin provided robust protection to vulnerable DA neurons in a culture paradigm in which these neurons die spontaneously and selectively as they mature. The efficacy of lactoferrin was comparable to that of glial cell line-derived neurotrophic factor, a prototypical neurotrophic factor for DA neurons. Neuroprotection by lactoferrin was attributable to its binding to heparan sulfate proteoglycans on the cell surface of DA neurons and subsequently to partial inactivation of focal adhesion kinase (FAK), a major effector kinase of integrins. We established that FAK inactivation served to unmask a prosurvival phosphoinositide 3-kinase/AKT-dependent signaling pathway that stimulates calcium shuttling from endoplasmic reticulum to mitochondria. DA neurons exposed to the mitochondrial toxin 1-methyl-4-phenylpyridinium were also partially protected by lactoferrin, further supporting the view that mitochondria may represent a downstream target for lactoferrin protective actions. Finally, we found that the iron binding capability of lactoferrin intervened in DA cell rescue only when neurodegeneration was consecutive to iron-catalyzed oxidative stress. Overall, our data suggest that the accumulation of lactoferrin in PD brains might be evidence of an attempt by the brain to minimize the consequences of neurodegeneration.

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Section: Resultsmentioning

confidence: 92%

The Iron-Binding Protein Lactoferrin Protects Vulnerable Dopamine Neurons from Degeneration by Preserving Mitochondrial Calcium Homeostasis

2013

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“…This hypothesis is supported by the ability of Lf to interact with heparan-sulfate-containing proteoglycans and with other components of the extracellular matrix (Zou et al 1992;Legrand et al 2008). In this regard, the binding of human Lf to the extracellular matrix proteins fibronectin and vitronectin (Sakamoto et al 2006), its association with proteoglycans in the PC12 cell line (Ishii et al 2007) and the interaction of bovine Lf with heparan-sulfate-containing proteoglycans on the cell surface (Ammendolia et al 2007) have all been described. Notably, the ability of Lf to interact with heparin and heparan sulfate and with other components of the extracellular matrix might mediate its extracellular diffusion in vivo (Thorne et al 2008).…”

Section: Discussionmentioning

confidence: 88%

Lactoferrin at basal side of mouse mammary epithelium derives in part from stroma cells

Pecorini¹,

Delpal²,

Truchet³

et al. 2009

Cell Tissue Res

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Lactoferrin is synthesized by glandular epithelial cells and neutrophils and is also present on both sides of the mammary epithelium. We have studied the origin of lactoferrin detected in the various compartments of mouse mammary tissue. As revealed by immunogold electron microscopy, lactoferrin is present in mammary epithelial cells and in the basal region of the epithelium, associated with connective tissue and stroma cells at all physiological stages studied. A perturbation of protein synthesis or transport after in vitro treatment with cycloheximide or brefeldin A does not abrogate lactoferrin labelling in the basal region of the epithelium. The expression of lactoferrin has also been observed in the fat pads of mammary glands from mice surgically depleted of epithelial cells. The sealing of one teat for 24 h is accompanied by an increase in both the number of stroma cells and the labelling of myoepithelial cells. Thus, the lactoferrin present in the interstitial space of the mouse mammary epithelium originates in part from stroma cells. Possible roles of lactoferrin at the basal side of the mammary epithelium are discussed.

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“…(34) In Prevotella nigrescens, a bacteria responsible of gingival diseases, a 40 kDa lactoferrin-binding protein has been purified from outer membrane and shown to possess a DING N terminus, but no other homology was reported ( (35) ; Table 1 and Fig. 1).…”

Section: More Ding Proteinsmentioning

confidence: 97%

The DING family of proteins: ubiquitous in eukaryotes, but where are the genes?

et al. 2009

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PstS and DING proteins are members of a superfamily of secreted, high-affinity phosphate-binding proteins. Whereas microbial PstS have a well-defined role in phosphate ABC transporters, the physiological function of DING proteins, named after their DINGGG N termini, still needs to be determined. PstS and DING proteins co-exist in some Pseudomonas strains, to which they confer a highly adhesive and virulent phenotype. More than 30 DING proteins have now been purified, mostly from eukaryotes. They are often associated with infections or with dysregulation of cell proliferation. Consequently, eukaryotic DING proteins could also be involved in cell-cell communication or adherence. The ubiquitous presence in eukaryotes of proteins structurally and functionally related to bacterial virulence factors is intriguing, as is the absence of eukaryotic genes encoding DING proteins in databases. DING proteins in eukaryotes could originate from unidentified commensal or symbiotic bacteria and could contribute to essential functions. Alternatively, DING proteins could be encoded by eukaryotic genes sharing special features that prevent their cloning. Both hypotheses are discussed.

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Interaction of Human Lactoferrin with Cell Adhesion Molecules through RGD Motif Elucidated by Lactoferrin-binding Epitopes

Cited by 41 publications

References 26 publications

The Iron-Binding Protein Lactoferrin Protects Vulnerable Dopamine Neurons from Degeneration by Preserving Mitochondrial Calcium Homeostasis

The Iron-Binding Protein Lactoferrin Protects Vulnerable Dopamine Neurons from Degeneration by Preserving Mitochondrial Calcium Homeostasis

Lactoferrin at basal side of mouse mammary epithelium derives in part from stroma cells

The DING family of proteins: ubiquitous in eukaryotes, but where are the genes?

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