Anion exchanger1 (AE1/SLC4A1) function is impaired in red blood cells from prediabetic subjects: Potential benefits of finger lime (Citrus australasica, Faustrime cultivar) juice extract
Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia‐induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capa...
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| Published in | Cell biochemistry and function Vol. 42; no. 6; pp. e4105 - n/a |
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| Main Authors | , , , , , , , , , , |
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| Abstract | Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia‐induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (SLC4A1), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (Citrus australasica, Faustrime cultivar) in counteracting oxidative stress‐related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/β‐spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition.
SIGNIFICANCE STATEMENT
The data obtained here reveal that structural and functional alterations related to the increase of oxidative stress and/or glycation events can still be reversible and the early application of bioactive molecules could counteract the majority of derangements in prediabetic RBCs. This study identifies finger lime as an antioxidant/anti‐glycation functional food and suggests that diet supplementation with finger lime might contribute to the prevention or attenuation of pathophysiological events linked to RBC dysfunction during the prediabetic condition. Additionally, our findings proved that measurement of anion exchange capability via AE1 remains a valid tool for monitoring the impact of oxidative stress/glycation on human RBC and systemic homeostasis. |
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| AbstractList | Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia‐induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (
SLC4A1
), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (
Citrus australasica
, Faustrime cultivar) in counteracting oxidative stress‐related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/β‐spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition.
The data obtained here reveal that structural and functional alterations related to the increase of oxidative stress and/or glycation events can still be reversible and the early application of bioactive molecules could counteract the majority of derangements in prediabetic RBCs. This study identifies finger lime as an antioxidant/anti‐glycation functional food and suggests that diet supplementation with finger lime might contribute to the prevention or attenuation of pathophysiological events linked to RBC dysfunction during the prediabetic condition. Additionally, our findings proved that measurement of anion exchange capability via AE1 remains a valid tool for monitoring the impact of oxidative stress/glycation on human RBC and systemic homeostasis. Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia‐induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (SLC4A1), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (Citrus australasica, Faustrime cultivar) in counteracting oxidative stress‐related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/β‐spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition. Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia‐induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (SLC4A1), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (Citrus australasica, Faustrime cultivar) in counteracting oxidative stress‐related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/β‐spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition. SIGNIFICANCE STATEMENT The data obtained here reveal that structural and functional alterations related to the increase of oxidative stress and/or glycation events can still be reversible and the early application of bioactive molecules could counteract the majority of derangements in prediabetic RBCs. This study identifies finger lime as an antioxidant/anti‐glycation functional food and suggests that diet supplementation with finger lime might contribute to the prevention or attenuation of pathophysiological events linked to RBC dysfunction during the prediabetic condition. Additionally, our findings proved that measurement of anion exchange capability via AE1 remains a valid tool for monitoring the impact of oxidative stress/glycation on human RBC and systemic homeostasis. Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia-induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (SLC4A1), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (Citrus australasica, Faustrime cultivar) in counteracting oxidative stress-related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/β-spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition.Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia-induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (SLC4A1), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (Citrus australasica, Faustrime cultivar) in counteracting oxidative stress-related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/β-spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition. |
| Author | Remigante, Alessia Dossena, Silvia Marino, Angela Russo, Marina Spinelli, Sara Gambardella, Lucrezia Straface, Elisabetta Dugo, Paola Caruso, Daniele Cafeo, Giovanna Morabito, Rossana |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39096031$$D View this record in MEDLINE/PubMed |
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| Keywords | glycation red blood cells anion exchanger 1 (SLC4A1) hyperglycemia oxidative stress |
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| Snippet | Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia‐induced... Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia-induced... |
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| SubjectTerms | Adult Anion exchange Anion Exchange Protein 1, Erythrocyte - metabolism anion exchanger 1 (SLC4A1) Anion exchanging Antioxidants Antioxidants - chemistry Antioxidants - metabolism Antioxidants - pharmacology Bioactive compounds Biological activity Biomarkers Cardiovascular diseases Catalase Cellular structure Citrus - chemistry Citrus australasica Citrus fruits Condition monitoring Cultivars Diabetes mellitus Dietary supplements Erythrocytes Erythrocytes - drug effects Erythrocytes - metabolism Female Fruit and Vegetable Juices - analysis Functional foods & nutraceuticals Glutathione glycation Glycosylation Hemoglobin Homeostasis Humans Hyperglycemia Juices Lipid peroxidation Lipids Male Methemoglobin Middle Aged Molecular modelling Oxidation Oxidation resistance Oxidative stress Oxidative Stress - drug effects Peroxidation Plant Extracts - chemistry Plant Extracts - pharmacology Prediabetic State - drug therapy Prediabetic State - metabolism Prevention red blood cells Spectrin Structure-function relationships Superoxide dismutase |
| Title | Anion exchanger1 (AE1/SLC4A1) function is impaired in red blood cells from prediabetic subjects: Potential benefits of finger lime (Citrus australasica, Faustrime cultivar) juice extract |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcbf.4105 https://www.ncbi.nlm.nih.gov/pubmed/39096031 https://www.proquest.com/docview/3096808709 https://www.proquest.com/docview/3087562724 |
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