Lactoferrin uptake by the rat liver. Characterization of the recognition site and effect of selective modification of arginine residues (original) (raw)

The binding of human lactoferrin to mouse peritoneal cells

Journal of Experimental Medicine, 1976

Human iron-saturated Lf (FeLf), which was labeled with 125I or 50Fe, was found to combine with the membrane of mouse peritoneal cells (MPC) which consisted of 70% macrophages. The following experimental data suggested the involvement of a specific receptor. (a) The binding of FeLf to MPC reached a saturation point. (b) The binding of radioactive FeLf was inhibited by preincubating the cells with cold FeLf but not with human Tf, human aggregated and nonaggregated IgG, or beef heart cytochrome c (c) Succinylation and carbamylation of FeLf resulted in a loss of its inhibiting activity on the binding of radioactive FeLf. Removal of neuraminic acid from FeLf increased its inhibitory activity. (d) The ability of apoLf to inhibit the binding of FeLf to MPC was significantly lower than that of FeLf. The existence of a Lf receptor capable of concentrating Lf released from neutrophils on the membrane of macrophages could explain the apparent blockade of the release of iron from the reticuloen...

The Biological Properties of Lactoferrin

Central European Journal of Sport Sciences and Medicine, 2016

Lactoferrin (LF) is an iron-binding glycoprotein from the transferrin family, which has been identified in most biological fluids as secretions from exocrine glands and the content of specific granules of neutrophils. It has been reported to have numerous functions. Due to antimicrobial and anti-inflammatory activity, the lactoferrin plays significant role in host defense against infection and extreme inflammation. Recent studies have also demonstrated that LF can protect against cancer in experimental animals and has anticarcinogenic activity in many human tumors. At the cellular level, LF modulates the proliferation, differentiation, maturation, activation, migration and function of immune cells. This review presents the multifunctional roles and specific beneficial properties of lactoferrin.

Apoptotic effects of bovine apo-lactoferrin on HeLa tumor cells

Cell biochemistry and function, 2017

Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12.5 μM). Western blot analysis showed that key apoptotic regulators including Bax, Bcl-2, Sirt1, Mcl-1, and PARP-1 were modulated by 1.25 μM of apo-bLf. In the same cell line, apo-bLf induced apoptosis together with poly (ADP-ribose) polymerase cleavage, caspase activation, and a significant drop of NAD(+) . In addition, apo-bLf-treated HeLa cells showed a marked increase of reactive oxygen species level and a significant GSH deplet...

Iron-binding fragments from the N-terminal and C-terminal regions of human lactoferrin

Biochemical Journal, 1978

Digestion of lactoferrin with pepsin at pH3.0 gave an iron-binding half-molecule that represents the C-terminal part of the native protein. Tryptic or chymotryptic digestion of 30%-iron-saturated lactoferrin yielded the N- and C-terminal half molecules, which could be separated by DEAE-Sephadex chromatography. The N- and C-terminal fragments did not show any immunological cross-reaction. The carbohydrate of lactoferrin was distributed equally between the two fragments.

Expression of lactoferrin in human stomach

International Journal of Cancer, 1991

The expression of the haeme-binding protein, lactoferrin, was studied in human gastric tissues displaying normal, benign hyperplastic or malignant histology. A single 2.5-kb mRNA was detected in only 14% (2/14) of normal resections. This was similar to the finding that 85% of tumoun were also negative, with 4/27 positive. In contrast, samples with superficial or atrophic gastritis had a high frequency of expression, with 5/7 and 9 / 14 positive respectively. The higher incidence of lactoferrin mRNA in antral samples was a reflection of the greater proportion of these compared with body resections of patients with gastritis. No expression was seen in any of 5 gastric carcinoma cell lines. High levels were observed in the cardia, in contrast to complete absence in the oesophagus. Immunocytochemistry showed localization of lactoferrin in cells of both antral and body glands. Chief cells, but not adjacent parietal cells, were strongly stained. In tissues exhibiting superficial or atrophic gastritis we observed a greater degree and intensity of staining as compared with samples with normal histology. We also observed some staining of tumour cells, though this was very patchy. Lactoferrin may have a role in mucosal iron transport in both normal and highly proliferating tissue, but does not appear to be significantly associated with malignant lesions.

Lactoferrin: potential functions, pharmacological insights, and therapeutic promises

Journal of Advanced Biotechnology and Experimental Therapeutics, 2021

ABSTRACT: Lactoferrin (LF) is an iron-binding multifunctional glycoprotein, act as a natural protective agent. In general, LF is involved in various physiological activities, including antibacterial, antifungal, antiviral, antiparasitic, anticarcinogenic and iron metabolism. The LF is most frequently found in milk as well as many other exocrine secretions such as saliva, bronchial mucus, seminal fluids, and gastrointestinal fluids, respectively. Increased expression and secretion of LF may play a significant role in the first line of host defense. One of the primary functions of LF is to scavenge free iron in fluids and inflamed areas to avoid free radical-facilitated damage. LF influences the proliferation, maturation, and activity of immune cells at the cellular level. LF plays a significant protective role in inflammation, oxidative stress, fibrosis, endoplasmic reticulum (ER) stress, autophagy dysfunction, and mitochondrial dysfunction. Also, LF was found protective against various pathologies including anemia, sepsis, and diarrhoea in clinical settings. This article reviews the protective role of LF against different pathophysiological conditions and its therapeutic advances as well as further research prospects.

Lactoferrin specifically inhibits endocytosis of chylomicron remnants but not α-macroglobulin

Journal of Biological Chemistry

Our recently found nonlipoprotein inhibitor of chylomicron remnant uptake, lactoferrin, has been investigated in vivo and in vitro. Lipoprotein lipase extracted triglycerides from chylomicrons, doubly labeled with [3H]retinol/[14C]oleate, in the presence of lactoferrin normally. The subsequent uptake of remnants into liver was retarded considerably. In the intact rat, chylomicron remnants (CRs), predominantly labeled in the apoB48 moiety by 125I, were excluded from the hepatic endosomal compartment in the presence of lactoferrin as shown in subcellular fractionation studies of rat livers. In tissue culture, internalization of [125I]chylomicron remnants was inhibited in the presence of 14 pM lactoferrin by 70%. Upon removal of lactoferrin, internalization was rapidly restored. Protease digestion eliminated the inhibitory effect completely. Modification of arginine residues with cyclohexanedione reversibly removed the inhibitory potency of lactoferrin. We located by molecular modeling...

Lactoferrin as a gene delivery vehicle to hepatocytes

Experimental & Molecular Medicine, 1997

Using lactoferrin as the specific ligand, we developed a simplified method for preparation of molecular conjugate for gene delivery. Replacement of column chromatography and dialysis by one step centrifugal filtration (Centricon, cut off size : 30,000), resulted in the rapid purification of bovine lactoferrin/polylysine (bLf/pL) and human lactoferrin/polylysine (hLf/ pL) conjugates and easy separation of unconjugated polylysine. The Lf/pL conjugates prepared by this method efficiently transferred the reporter genes, CAT and LacZ gene, to HeLa and hepatic cells. The bLf/pL and hLf/pL conjugates could transfer the reporter genes to various hepatocytes including primary mouse hepatocyte, Hepa 1-6, SK-Hep1 and Chang liver, but not to NIH 3T3 mouse fibroblast cells, indicating that the Lf/pL conjugates conferred hepatocyte-specific gene transfer. The bLf/pL and hLf/pL conjugates prepared in the present study exhibited higher transfection efficiencies for mouse and human hepatocytes than the commercially available transferrin/polylysine (Tf/pL) conjugate.