Effector-induced Syk-mediated phosphorylation in human erythrocytes

Bordin, Luciana; Ion-Popa, Florina; Brunati, Anna Maria; Clari, Giulio; Low, Philip S.

doi:10.1016/j.bbamcr.2004.12.010

Cited by 42 publications

(59 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In diseased red cells, we observed an increase of band 3 tyrosine phosphorylation, most likely due to increased membrane association of Syk and Lyn kinases which have already been reported to tyrosine-phosphorylate band 3. [30][31][32] In addition, changes in the tyrosinephosphorylation of band 4.1, band 4.2, and stomatin were evident in diseased red cells and were independent of the adaptive mechanisms to cell swelling ( Figure 5), suggesting a perturbation of intracellular signaling pathways toward the membrane-cytoskeleton network. 22,[33][34][35] Previous studies in skate red cells have shown that volume expansion is associated with increased Syk and Lyn activity and changes in phosphorylation state of various membrane proteins and in their association with membrane lipid rafts.…”

Section: Discussionmentioning

confidence: 99%

A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis

Iolascon¹,

Falco²,

Borgèse³

et al. 2009

Haematologica

View full text Add to dashboard Cite

Background \ud \ud Stomatocytoses are a group of inherited autosomal dominant hemolytic anemias and include overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis, hereditary cryohydrocytosis and familial pseudohyperkalemia. \ud \ud Design and Methods \ud \ud We report a novel variant of hereditary stomatocytosis clue to a de novo band 3 mutation (p. G796R-band3 CEINGE) associated with a dyserythropoietic phenotype. Band 3 genomic analysis, measurement at of hematologic parameters and red cell indices and morphological analysis of bone marrow were carried out. We then evaluated the red cell membrane permeability and ion transport systems by functional studies of the patients erythrocytes and Xenopus oocytes transfected with mutated band 3. We analyzed the red cell membrane tyrosine phosphorylation profile and the membrane association of the tyrosine kinases Syk and Lyn from the Src-family-kinase group, since the activity of the membrane cation transport pathways is related to cyclic phosphorylation-dephosphorylation events. \ud \ud Results \ud \ud The patient showed mild hemolytic anemia with circulating stomatocytes together with signs of dyserythropoiesis. Her red cells displayed increased Na(+) content with decreased K(+) content and abnormal membrane cation transport activities. Functional characterization of band 3 CEINGE in Xenopus oocytes showed that the mutated band 3 is converted from being an anion exchanger (Cl(-), HCO(3)(-)) to being a cation pathway for Na(+) and K(+). Increased tyrosine phosphorylation of some red cell membrane proteins was observed in diseased erythrocytes. Syk and Lyn membrane association was increased in the patient's red cells compared to in normal controls, indicating perturbation of phospho-signaling pathways involved in cell volume regulation events. \ud \ud Conclusions \ud \ud Band 3 CEINGE alters function from that of anion exchange to cation transport, affects the membrane tyrosine phosphorylation profile, in particular of band 3 and stomatin, and its presence during red cell development likely contributes to dyserythropiesis

show abstract

Section: Discussionmentioning

confidence: 99%

A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis

Iolascon¹,

Falco²,

Borgèse³

et al. 2009

Haematologica

View full text Add to dashboard Cite

show abstract

“…Syk kinase has been widely studied as a therapeutic target in inflammation [59], neurodegenerative disorders [60], allergy [61] and cancer [62][63][64]. Besides the studies performed in erythrocytes [26,27,65], the role of cysteine oxidation on Syk activity and functions in T cells are still unknown.…”

Section: Introductionmentioning

confidence: 99%

T cell tyrosine phosphorylation response to transient redox stress

Secchi

Carta

Crescio

et al. 2015

Cellular Signalling

View full text Add to dashboard Cite

Reactive Oxygen Species (ROS) are crucial to multiple biological processes involved in the pathophysiology of inflammation, and are also involved in redox signaling responses. Although previous reports have described an association between oxidative events and the modulation of innate immunity, a role for redox signaling in T cell mediated adaptive immunity has not been described yet. This work aims at assessing if T cells can sense redox stress through protein sulfhydryl oxidation and respond with tyrosine phosphorylation changes. Our data show that Jurkat T cells respond to -SH group oxidation with specific tyrosine phosphorylation events. The release of T cell cytokines TNF, IFNγ and IL2 as well as the expression of a number of receptors are affected by those changes. Additionally, experiments with spleen tyrosine kinase (Syk) inhibitors showed a major involvement of Syk in these responses. The experiments described herein show a link between cysteine oxidation and tyrosine phosphorylation changes in T cells, as well as a novel mechanism by which Syk inhibitors exert their anti-inflammatory activity through the inhibition of a response initiated by ROS.

show abstract

“…We recently demonstrated that diamide-treated erythrocytes express a well-defined tyrosine phosphorylation (Tyr-P) level of membrane proteins, particularly of band 3 (20). Alterations in band 3 Tyr-P levels represent preexisting modifications of membrane status, like that observed in glucose-6-phosphate dehydrogenase (G6PD)-deficient patients (18,21) suffering from chronic impairment of antioxidant defenses or in endometriotic women (22) with systemic inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…Alterations in band 3 Tyr-P levels represent preexisting modifications of membrane status, like that observed in glucose-6-phosphate dehydrogenase (G6PD)-deficient patients (18,21) suffering from chronic impairment of antioxidant defenses or in endometriotic women (22) with systemic inflammation. Diamide, a mild oxidant, affects the sulfhydryl groups of cysteines by inducing disulfide bond formation and triggers band 3 Tyr-P (16,17,18,20,21,22), which is a useful parameter in the evaluation of oxidation-related damage to cells (18,21,22). We also observed that, while diamide treatment reduced total glutathione (GSH) contents detectable in the cytosol of endometriotic patients, normal subjects were unaffected, and the differences between GSH content before and after diamide treatment were defined as DGSH, an additional parameter of inflammatory status in endometriosis (22).…”

Section: Introductionmentioning

confidence: 99%

Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome

Donà¹,

Sabbadin²,

Fiore³

et al. 2012

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Objective: Possibly due to a deficiency of insulin mediators, polycystic ovary syndrome (PCOS) is often associated with insulin resistance (IR) and hyperinsulinemia, likely responsible for an elevated production of reactive oxygen species. We investigated oxidative-related alterations in erythrocytes and anti-inflammatory effects of inositol in women with PCOS before and after treatment with myo-inositol (MYO). Methods: Twenty-six normal-weight PCOS patients were investigated before and after MYO administration (1200 mg/day for 12 weeks; nZ18) or placebo (nZ8) by evaluating serum testosterone, serum androstenedione, fasting serum insulin, fasting serum glucose, insulin area under the curve (AUC), and glucose AUC after oral glucose tolerance test and homeostasis model of assessment-IR. In erythrocytes, band 3 tyrosine phosphorylation (Tyr-P) level, glutathione (GSH) content, and glutathionylated proteins (GSSP) were also assessed. Results: Data show that PCOS patients' erythrocytes underwent oxidative stress as indicated by band 3 Tyr-P values, reduced cytosolic GSH content, and increased membrane protein glutathionylation. MYO treatment significantly improved metabolic and biochemical parameters. Significant reductions were found in IR and serum values of androstenedione and testosterone. A significant association between band 3 Tyr-P levels and insulin AUC was found at baseline but disappeared after MYO treatment, while a correlation between band 3 Tyr-P and testosterone levels was detected both before and after MYO treatment. Conclusions: PCOS patients suffer from a systemic inflammatory status that induces erythrocyte membrane alterations. Treatment with MYO is effective in reducing hormonal, metabolic, and oxidative abnormalities in PCOS patients by improving IR.

show abstract

Effector-induced Syk-mediated phosphorylation in human erythrocytes

Cited by 42 publications

References 31 publications

A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis

A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis

T cell tyrosine phosphorylation response to transient redox stress

Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome

Contact Info

Product

Resources

About