Lactoferrin-Protector against Oxidative Stress and Regulator of Glycolysis in Human Erythrocytes

Abstract

Fe-lactoferrin to its receptors. Lactoferrin (50 and 100 nm), similar to ferricyanide, increased the accumulation of lactate (respectively by 25% and 30%). These results support the assumption that ferricyanide and lactoferrin are final acceptors of a common electron transport chain connected with the regulation of glycolysis. We established an antioxidative effect of lactoferrin on erythrocytes, which was expressed as: a) an influence on content and on activity of intracellular antioxidants Ð namely an enhancement of the content of reduced glutathione; b) a decreased content both of products of lipid peroxidation (thiobarbituric acid reactive substances) and hemolysis under normal conditions and oxidative stress. Lactoferrin is capable to bind metal ions and thus to block their catalytic participation in the oxidative disturbances of the membrane. In most of our experiments there were no metal ions in the incubation mixtures (except those stimulating oxidative stress). Our results showed that Lf limited both the generation of thiobarbituric acid reactive substances and hemolysis in the absence of metal ions in the media, as well as in their presence. These facts suggest that probably the antioxidative property of lactoferrin is glycolysis stimulation, leading to increased formation of ATP, which is necessary to maintain the ion gradient, membrane potential and morphology of the erythrocyte.

Lactoferrin increases 172ThrAMPK phosphorylation and insulin-induced p473SerAKT while impairing adipocyte differentiation

“…Its antioxidant 20 and anti-inflammatory activities (blocking nuclear factor-kB activation in response to LPS 16 ) could explain the positive effects of lactoferrin in intracellular insulin action. LPS-stimulated THP-1 conditioned media induced a significant decrease in response to insulin in HepG2, 3T3-L1 fibroblasts and in pre-differentiated (after INS-DEX-IBM mixture) 3T3-L1 cells, as demonstrated by decreased insulin-induced 473Ser AKT phosphorylation.…”

Effects of a natural extract from Mangifera indica L, and its active compound, mangiferin, on energy state and lipid peroxidation of red blood cells

“…Indeed, a large number of previous studies has also reported enhanced protection by polyphenols on RBC [36]. Plant-derived phenols are reported to have a broad spectrum of free-radical scavenging, antioxidant and protective activities [37][38][39][40][41]. In other studies red wine polyphenols, containing 3.5 mM gallic acid equivalent (GAE) of phenolic compounds, prevented oxidative modifications on the RBC system, such as haemolysis and lipid peroxidation.…”

Protein Kinases and Protein Phosphatases as Participants in Signal Transduction of Erythrocytes

“…There are experiment-based evidence for the existence of erythrocyte e-transport transmembrane chain related to transferrin receptor (Orringer and Roer, 1979;Goldenberg et al 1990), that is known to reduce K 3 Fe(CN) 6 and removes protons from inside the cell through the cell membrane (Low et al 1987). Our own experiments showed that K 3 Fe(CN) 6 inhibits 59 FeLF binding to erythrocytes (Maneva et al 2003) as most probably Lf and K 3 Fe(CN) 6 compete for one and the same electron formed in oxidative phosphorylation in glycolysis; Lf is the physisological activator of the signal pathway used by ferricyanide that leads to tyrosine phosphorylation of band 3 and consequent glycolysis activation.…”

“…Our previous studies showed that Lf binding with erythrocyte membrane receptors (Taleva et al, 1999) results in stimulation of glycolysis, antioxidative protection (Maneva et al, 2003) and activation of Na + /K + -ATPase activity (Maneva et al, 2007). Lf-receptor interaction might intervene in short-term effects of regulation, involving processes of changes in association, phosphorylation and oxidation of the membrane proteins.…”

“…Like insulin, Lf also activates Na + /H + -antiport (Sun et al 1991) and stimulates the lactate formation (Maneva et al 2003). Therefore, it could be suggested that Lf uses the same PI3K -dependent mechanism for glycolysis activation (Boivin, 1988); 2) Phosphorylation of tyrosin residues in band 3 (Boivin, 1988) leads to dissociation of the complex with glycolytic enzymes, leading to their activation (Low et al 1993).…”