Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia

Sokolov, A. V.; Dubrovskaya, N. М.; Kostevich, Valeria A.; Vasilev, D. S.; Voynova, Irina V.; Захарова, Е. М.; Runova, O. L.; Semak, Igor; Будевич, А. И.; Nalivaeva, Natalia N.; Vasilyev, V. B.

doi:10.3390/nu14071399

Cited by 11 publications

(7 citation statements)

References 53 publications

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“…With such a set of influences, the following can be observed: (1) chemical modification of amino acid residues; (2) fragmentation of the polypeptide chain; (3) change in the tertiary and secondary structure of BSA molecules; (4) partial denaturation; and (5) aggregation of molecules [ 36 , 37 , 38 , 39 ]. It should be noted that a similar set of events occurs with proteins under the action of oxidative stress [ 40 ], which develops in living systems under the action of various physical and chemical factors [ 41 ], during the development of inflammation [ 42 ], hypoxia [ 43 ], and a number of diseases [ 44 ], etc.…”

Section: Discussionmentioning

confidence: 99%

Effect of Laser-Induced Optical Breakdown on the Structure of Bsa Molecules in Aqueous Solutions: An Optical Study

et al. 2022

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The influence of laser radiation of a typical surgical laser on the physicochemical properties of the Bovine Serum Albumin (BSA) protein was studied. It was established that the physicochemical characteristics of optical breakdown weakly depend on the concentration of protein molecules. At the same time, the patterns observed for an aqueous solution of BSA irradiated with a laser for different time periods were extremely similar to the classical ones. It was established that after exposure to laser radiation, the optical density of protein solutions increases. At the same time, the intensity of BSA fluorescence due to aromatic amino acid residues decreases insignificantly after exposure to laser radiation. In this case, the position of the excitation and emission maximum does not change, and the shape of the fluorescence spot on 3D maps also does not change significantly. On the Raman spectrum after exposure to laser radiation, a significant decrease in 1570 cm−1 was observed, which indicates the degradation of α-helices and, as a result, partial denaturation of BSA molecules. Partial denaturation did not significantly change the total area of protein molecules, since the refractive index of solutions did not change significantly. However, in BSA solutions, after exposure to laser radiation, the viscosity increased, and the pseudoplasticity of aqueous solutions decreased. In this case, there was no massive damage to the polypeptide chain; on the contrary, when exposed to optical breakdown, intense aggregation was observed, while aggregates with a size of 400 nm or more appeared in the solution. Thus, under the action of optical breakdown induced by laser radiation in a BSA solution, the processes of partial denaturation and aggregation prevail, aromatic amino acid residues are damaged to a lesser extent, and fragmentation of protein molecules is not observed.

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Section: Discussionmentioning

confidence: 99%

Effect of Laser-Induced Optical Breakdown on the Structure of Bsa Molecules in Aqueous Solutions: An Optical Study

et al. 2022

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“…Considering that replication cycle of SARS-CoV-2 mediated by TfR1 endocytosis can alter normal Tf-mediated influx of iron, it is not surprising that COVID-19-associated dysregulations of iron and oxygen metabolism, such as low levels of serum iron and erythropoietin accompanied by high levels of ferritin and hepcidin, can be corrected by Lf (Suriawinata and Mehta 2022 ). Anti-anemic and anti-hypoxic effects of Lf associated with down-regulation of IL-6 and hepcidin (Cutone et al 2014 ; Rosa et al 2017 ; Lepanto et al 2019 ; Artym et al 2021 ) and up-regulation of erythropoietin and ceruloplasmin (Pulina et al 2010 ; Zakharova et al 2012 , 2018 ; Bonaccorsi di Patti et al 2018 ; Kostevich et al 2016 ; Sokolov et al 2022b ) seem to be a promising strategy for treating COVID-19 complications. It is worth noting that one of the first papers dedicated to the protective effect of Lf against SARS-CoV-2 infection also described the studies of antiviral effect of hypoxia, which decreased the content of heparan sulphate on cell surface by downregulating syndecan-1 expression via hypoxia-inducible factor-1 alpha (HIF-1α)-dependent mechanism (Prieto-Fernández et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…We pursued this area of research by testing the effect of TfR1 degradation on infection of Vero cells by SARS-CoV-2. Thus, we observed dose-dependent inhibition of SARS-CoV-2 replication (IC 50 ~ 6–40 μM), as well as abrogated endocytosis of the receptor-binding domain (RBD) of Spike protein after treatment of cell culture with ferristatin II (Sokolov et al 2022a , b ). This compound induced degradation of TfR1 (Byrne et al 2013 ), and was initially discovered in screening small-size inhibitors of iron influx into cancer cells (Brown et al 2004 ).…”

Section: Introductionmentioning

confidence: 91%

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin

et al. 2022

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The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R 2 > 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by K D to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1–4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed. Supplementary Information The online version contains supplementary material available at 10.1007/s10534-022-00458-6.

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“…Apo-Lf injected animals showed a 40% increased lifespan; the authors attributed the results to the ability of apo-Lf to stabilize hypoxia-inducible factor 1-alpha (HIF-1α) expression. Sokolov and colleagues (2022) administered 10 mg/kg of recombinant human Lf before or after a hypoxic episode during lactation and observed preserved cognitive function in rats’ offspring subjected to prenatal hypoxia [ 100 ]. Following HI in three-day-old rats, Lf-supplemented animals showed decreased cortical loss, hypomyelination and preserved diffusivity parameters assessed by MRI at postnatal day 25 [ 97 ].…”

Section: Lactoferrin For Preventing Iugr/premature Delivery and Assoc...mentioning

confidence: 99%

Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan

2022

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Early adverse fetal environments can significantly disturb central nervous system (CNS) development and subsequently alter brain maturation. Nutritional status is a major variable to be considered during development and increasing evidence links neonate and preterm infant impaired brain growth with neurological and psychiatric diseases in adulthood. Breastfeeding is one of the main components required for healthy newborn development due to the many “constitutive” elements breastmilk contains. Maternal intake of specific nutrients during lactation may alter milk composition, thus affecting newborn nutrition and, potentially, brain development. Lactoferrin (Lf) is a major protein present in colostrum and the main protein in human milk, which plays an important role in the benefits of breastfeeding during postnatal development. It has been demonstrated that Lf has antimicrobial, as well as anti-inflammatory properties, and is potentially able to reduce the incidence of sepsis and necrotizing enterocolitis (NEC), which are particularly frequent in premature births. The anti-inflammatory effects of Lf can reduce birth-related pathologies by decreasing the release of pro-inflammatory factors and inhibiting premature cervix maturation (also related to commensal microbiome abnormalities) that could contribute to disrupting brain development. Pre-clinical evidence shows that Lf protects the developing brain from neuronal injury, enhances brain connectivity and neurotrophin production, and decreases inflammation in models of perinatal inflammatory challenge, intrauterine growth restriction (IUGR) and neonatal hypoxia-ischemia (HI). In this context, Lf can provide nutritional support for brain development and cognition and prevent the origin of neuropsychiatric diseases later in life. In this narrative review, we consider the role of certain nutrients during neurodevelopment linking to the latest research on lactoferrin with respect to neonatology. We also discuss new evidence indicating that early neuroprotective pathways modulated by Lf could prevent neurodegeneration through anti-inflammatory and immunomodulatory processes.

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Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia

Cited by 11 publications

References 53 publications

Effect of Laser-Induced Optical Breakdown on the Structure of Bsa Molecules in Aqueous Solutions: An Optical Study

Effect of Laser-Induced Optical Breakdown on the Structure of Bsa Molecules in Aqueous Solutions: An Optical Study

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin

Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan

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