Aging Injury Impairs Structural Properties and Cell Signaling in Human Red Blood Cells; Açaì Berry Is a Keystone

Abstract

Red blood cell (RBC) deformability is the ability of cells to modulate their shape to ensure transit through narrow capillaries of the microcirculation. A loss of deformability can occur in several pathological conditions, during natural RBC aging through an increase in membrane protein phosphorylation, and/or through the structural rearrangements of cytoskeletal proteins due to oxidative conditions, with a key role played by band 3. Due to the close relationship between aging and oxidative stress, flavonoid-rich foods are good candidates to counteract age-related alterations. This study aims to verify the beneficial role of Açaì extract in a d-Galactose (d-Gal)-induced model of aging in human RBCs. To this end, band 3 phosphorylation and structural rearrangements in membrane cytoskeleton-associated proteins, namely spectrin, ankyrin, and/or protein 4.1, are analyzed in RBCs treated with 100 mM d-Gal for 24 h, with or without pre-incubation with 10 μg/mL Açaì extract for 1 h. Furthermore, RBC deformability is also measured. Tyrosine phosphorylation of band 3, membrane cytoskeleton-associated proteins, and RBC deformability (elongation index) are analyzed using western blotting analysis, FACScan flow cytometry, and ektacytometry, respectively. The present data show that: (i) Açaì berry extract restores the increase in band 3 tyrosine phosphorylation and Syk kinase levels after exposure to 100 mM d-Gal treatment; and (ii) Açaì berry extract partially restores alterations in the distribution of spectrin, ankyrin, and protein 4.1. Interestingly, the significant decrease in membrane RBC deformability associated with d-Gal treatment is alleviated by pre-treatment with Açaì extract. These findings further contribute to clarify mechanisms of natural aging in human RBCs, and propose flavonoid substances as potential natural antioxidants for the treatment and/or prevention of oxidative-stress-related disease risk.

Red Blood Cell Deformability Is Expressed by a Set of Interrelated Membrane Proteins

“…As a mechanical property, RBC deformability depends on the cell membrane structure and composition, and their alteration should thereby correlate with changes in biochemical measures. Previous studies, both experimental and numerical simulations, linked the cell deformability to the content of specific membrane proteins, particularly stomatin, band-3, and protein 4.1R [ 37 , 38 , 39 , 40 ].…”

AAPH-induced oxidative damage reduced anion exchanger 1 (SLC4A1/AE1) activity in human red blood cells: protective effect of an anthocyanin-rich extract

“…These results indicate that anthocyanins can prevent but not reverse an oxidative stress-induced loss of cell membrane integrity. Red blood cells membrane mechanical properties can be remodeled by oxidative stress, thus resulting in a reduction of deformability, or alternatively, in altered permeability of the phospholipid bilayer, which, in turn, limits plasma membrane ability to counter osmotic variations ( Spinelli et al, 2023 ). Among the main determinants of RBC deformability ( Maruyama et al, 2022 ), the mean corpuscular volume (MCV, as a measure of cellular size) was considered.…”

“…These biochemical modifications may induce significant damage to the plasma membrane lipid components as well as protein structures. As a result, the membrane mechanical properties could be altered, resulting in a reduction of fluidity and deformability or altered permeability of the phospholipid bilayer, which, in turn, reduces the ability of the plasma membrane to withstand osmotic changes ( Spinelli et al, 2023 ). These data indicate that anthocyanins might behave synergistically with the endogenous antioxidant machinery to counteract oxidative stress events in mature RBCs and preserve cellular integrity.…”

Unveiling the Immunomodulatory Potential of Phenolic Compounds in Food Allergies

“…Recently, the use of phenolic compounds in the prevention and mitigation of symptoms of these pathologies has been proposed. Both the scientific community and the general population have asserted that the consumption of plant-based foods is good for overall human health, due to their anti-aging, anti-inflammatory and anti-microbial properties [ 13 , 14 , 15 , 16 ]. This has been in part attributed to the high concentration of phenolic compounds present in these foods.…”