Intracellular Retention and Subsequent Release of Bovine Milk Lactoferrin Taken Up by Human Enterocyte-Like Cell Lines, Caco-2, C2BBe1 and HT-29

Akiyama, Yuka; Oshima, Kenzi; Shin, Kouichirou; Wakabayashi, Hiroyuki; Abe, Fumiaki; Nadano, Daita; Matsuda, Tsukasa

doi:10.1271/bbb.121011

Cited by 17 publications

(15 citation statements)

References 32 publications

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“…3) In this study, to confirm the earlier published results, we have reevaluated LF uptake and release by Caco-2 cells. Unlike previous reports, 6) intact bLF, human LF (hLF) and its derivatives (N-lobe and Fc fusions) were found to be successfully taken up and released by Caco-2 cells. Thus, the molecular processes of LF uptake and release by Caco-2 cells can mimic the absorption of LF by the human small intestine.…”

Section: Introductioncontrasting

confidence: 76%

“…4) Previous studies have reported that LF can be taken up into Caco-2 cells via a clathrin-mediated endocytic process mediated by the human intestinal lactoferrin receptor (also called human intelectin-1). 5) Moreover, bovine LF (bLF) has been shown to be taken up into 10 d-cultured Caco-2 cells, after which degraded bLF is released back into the culture medium. 6) Another study used spontaneously differentiated cell monolayers of 21 d-cultured Caco-2 as an in vitro model of the intestinal barrier 4) and showed, using a permeability assay, that LF transported across Caco-2 monolayers was more likely to be degraded, 7,8) which was inconsistent with in vivo events.…”

Section: Introductionmentioning

confidence: 99%

“…5) Moreover, bovine LF (bLF) has been shown to be taken up into 10 d-cultured Caco-2 cells, after which degraded bLF is released back into the culture medium. 6) Another study used spontaneously differentiated cell monolayers of 21 d-cultured Caco-2 as an in vitro model of the intestinal barrier 4) and showed, using a permeability assay, that LF transported across Caco-2 monolayers was more likely to be degraded, 7,8) which was inconsistent with in vivo events. 3) In this study, to confirm the earlier published results, we have reevaluated LF uptake and release by Caco-2 cells.…”

Section: Introductionmentioning

confidence: 99%

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Cellular Uptake and Release of Intact Lactoferrin and Its Derivatives in an Intestinal Enterocyte Model of Caco-2 Cells

Matsuzaki

Nakamura

Nogita

et al. 2019

Biological & Pharmaceutical Bulletin

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An Intact form of lactoferrin (LF) is known to be absorbed from the small intestine and transported into the blood circulation. We reevaluated the cellular uptake and release of LF using an enterocyte model of human small intestinal cells derived from the Caco-2 cell line. In contrast to a previous report, we observed that intact bovine LF was taken up into seven and 21 d-cultured Caco-2 cells and successfully released back into the culture medium, even though the human intestinal LF receptor, intelectin-1, was not immunochemically detectable. Similar observations were made for human LF and its derivatives (the N-terminal half of LF designated N-lobe and Fc fusions). These observations regarding the uptake and release of intact LF in Caco-2 cells were consistent with in vivo observations. Therefore, we propose that the uptake and release of intact LF by Caco-2 cells should be assessed as a potential in vitro model of in vivo LF absorption in human intestines.

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Section: Introductioncontrasting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cellular Uptake and Release of Intact Lactoferrin and Its Derivatives in an Intestinal Enterocyte Model of Caco-2 Cells

Matsuzaki

Nakamura

Nogita

et al. 2019

Biological & Pharmaceutical Bulletin

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“…It has also been shown that bLF is taken up into the nucleus via bLF receptors in human enterocyte cell lines [23]. We therefore expect that the mechanism by which LF protects against radiation exposure, including gamma irradiation, is close to being elucidated.…”

Section: Discussionmentioning

confidence: 94%

Lactoferrin Directly Scavenges Hydroxyl Radicals and Undergoes Oxidative Self-Degradation: A Possible Role in Protection against Oxidative DNA Damage

Ogasawara

Imase

Oda³

et al. 2014

IJMS

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In this study, we examined the protective effect of lactoferrin against DNA damage induced by various hydroxyl radical generation systems. Lactoferrin (LF) was examined with regard to its potential role as a scavenger against radical oxygen species using bovine milk LF. Native LF, iron-saturated LF (holo-LF), and apolactoferrin (apo-LF) effectively suppressed strand breaks in plasmid DNA due to hydroxyl radicals produced by the Fenton reaction. In addition, both native LF and holo-LF clearly protected calf thymus DNA from fragmentation due to ultraviolet irradiation in the presence of H2O2. We also demonstrated a protective effect of all three LF molecules against 8-hydroxydeoxyguanosine (8-OHdG) formation in calf thymus DNA following ultraviolet (UV) irradiation with H2O2. Our results clearly indicate that native LF has reactive oxygen species-scavenging ability, independent of its nature as a masking component for transient metals. We also demonstrated that the protective effect of LF against oxidative DNA damage is due to degradation of LF itself, which is more susceptible to degradation than other bovine milk proteins.

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“…Their translation leads to Lf, an 80 kDa iron-binding protein widely distributed in biological fluids and also expressed by immune cells [9], [10] and to ΔLf, a 73 kDa intracellular protein in which the leader sequence and the first 25 amino acid residues of Lf are absent [11]. Both isoforms possess NLS motifs [12], [13] and the use of a GFP-ΔLf fusion protein clearly demonstrated that ΔLf targets the nucleus [3], [13], [14], [15] whereas the nuclear targeting of Lf is still controversial [3], [14], [16], [17], [18], [19]. Thus, uptake and nuclear targeting of Lf depend on its target cells and on the presence of specific mammalian receptors (LfRs) at their surfaces such as LRP, CD14, nucleolin and intelectin [16], [17].…”

Section: Introductionmentioning

confidence: 99%

SILAC-Based Proteomic Profiling of the Human MDA-MB-231 Metastatic Breast Cancer Cell Line in Response to the Two Antitumoral Lactoferrin Isoforms: The Secreted Lactoferrin and the Intracellular Delta-Lactoferrin

et al. 2014

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BackgroundLactoferrins exhibit antitumoral activities either as a secretory lactoferrin or an intracellular delta-lactoferrin isoform. These activities involve processes such as regulation of the cell cycle and apoptosis. While lactoferrin has been shown to exert its function by activating different transduction pathways, delta-lactoferrin has been proven to act as a transcription factor. Like many tumor suppressors, these two proteins are under-expressed in several types of cancer, particularly in breast cancer.Methodology/Principal FindingsIn order to compare the differential effects of the re-introduction of lactoferrin isoforms in breast cancer cells we chose the cancerous mammary gland MDA-MB-231 cell line as a model. We produced a cell line stably expressing delta-lactoferrin. We also treated these cells with fresh purified human breast lactoferrin. We performed two quantitative proteomic studies in parallel using SILAC coupled to mass spectrometry in order to compare the effects of different doses of the two lactoferrin isoforms. The proteome of untreated, delta-lactoferrin expressing and human lactoferrin treated MDA-MB-231 cells were compared. Overall, around 5300 proteins were identified and quantified using the in-house developed MFPaQ software. Among these, expression was increased by 1.5-fold or more for around 300 proteins in delta-lactoferrin expressing cells and 190 proteins in lactoferrin treated cells. At the same time, about 200 and 40 proteins were found to be downregulated (0-0.7-fold) in response to delta-lactoferrin and lactoferrin, respectively.Conclusions/SignificanceRe-introduction of delta-lactoferrin and lactoferrin expression in MDA-MB-231 mainly leads to modifications of protein profiles involved in processes such as proliferation, apoptosis, oxidative stress, the ubiquitin pathway, translation and mRNA quality control. Moreover, this study identified new target genes of delta-lactoferrin transcriptional activity such as SelH, GTF2F2 and UBE2E1.

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Intracellular Retention and Subsequent Release of Bovine Milk Lactoferrin Taken Up by Human Enterocyte-Like Cell Lines, Caco-2, C2BBe1 and HT-29

Cited by 17 publications

References 32 publications

Cellular Uptake and Release of Intact Lactoferrin and Its Derivatives in an Intestinal Enterocyte Model of Caco-2 Cells

Cellular Uptake and Release of Intact Lactoferrin and Its Derivatives in an Intestinal Enterocyte Model of Caco-2 Cells

Lactoferrin Directly Scavenges Hydroxyl Radicals and Undergoes Oxidative Self-Degradation: A Possible Role in Protection against Oxidative DNA Damage

SILAC-Based Proteomic Profiling of the Human MDA-MB-231 Metastatic Breast Cancer Cell Line in Response to the Two Antitumoral Lactoferrin Isoforms: The Secreted Lactoferrin and the Intracellular Delta-Lactoferrin

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