Membrane association of peroxiredoxin-2 in red cells is mediated by the N-terminal cytoplasmic domain of band 3

Mattè, Alessandro; Bertoldi, Mariarita; Mohandas, Narla; An, Xiuli; Bugatti, Antonella; Brunati, Anna Maria; Rusnati, Marco; Tibaldi, Elena; Siciliano, Angela; Turrini, Franco; Perrotta, Silverio; Franceschi, Lucia De

doi:10.1016/j.freeradbiomed.2012.10.543

Cited by 75 publications

(75 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is interesting to note that oxidation and subsequent dimerization of Prdx2 does seem to promote membrane-association of the protein as shown in human erythrocytes (32) and rat myocardium (33). As both monomer and dimer are present in unstimulated cells, but with little or no release in the absence of stimulation (10) (this study), it may be the ratio of monomer to dimer that determines the association of the dimer with the exosomes and subsequent export from the cell as postulated in Figure 8.…”

Section: Discussionmentioning

confidence: 99%

Cysteine Oxidation Targets Peroxiredoxins 1 and 2 for Exosomal Release through a Novel Mechanism of Redox-Dependent Secretion

Mullen

Hanschmann

Lillig

et al. 2015

Mol Med

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Cysteine Oxidation Targets Peroxiredoxins 1 and 2 for Exosomal Release through a Novel Mechanism of Redox-Dependent Secretion

Mullen

Hanschmann

Lillig

et al. 2015

Mol Med

View full text Add to dashboard Cite

“…14,[19][20][21] Red cell membrane (ghost) and cytosol fractions were obtained as previously reported. [22][23][24] Immunoblot 23, 25 and immunoprecipitation (IP) 14,[26][27][28] were carried out as previously reported (see supplemental Materials and methods for details). When required, the IP assays were carried out as required in the absence or presence of the GST-Lyn/SH3 domain or of the inhibitors PP2 or geldanamycin (GA).…”

Section: Red Cell Membrane Cytosol Preparation Immunoblot Analysismentioning

confidence: 99%

“…22,23,25,28,30 Syk-phosphorylated membranes were used as substrates, as described in De Franceschi et al 14 …”

Section: Phosphorylation Of Erythrocyte Membranesmentioning

confidence: 99%

“…14,27 Generation of potassium iodide-stripped, inside-out vesicles (KIOVs) Details are reported in supplemental Materials and methods. 23,31 Fractionation by centrifugation on glycerol gradient Cytosolic proteins from healthy and chorea-acanthocytosis red cells were loaded on a linear glycerol (10-40%) gradient as described in Trentin et al 32 The tubes were centrifuged 18 hours at 100 000g in a SW60Ti rotor (Beckman) at 4°C, and 18 fractions were collected from the top of each tube. 32 Computational structural modeling and protein-protein docking of Hsp90 and Lyn tyrosine kinase domain and in silico amino acid sequence analyses Details are reported in supplemental Materials and methods.…”

Section: In Vitro Kinase Assaymentioning

confidence: 99%

See 1 more Smart Citation

A new molecular link between defective autophagy and erythroid abnormalities in chorea-acanthocytosis

Lupo

Tibaldi

Mattè

et al. 2016

Blood

Self Cite

View full text Add to dashboard Cite

Key Points• In chorea-acanthocytosis, spiculated red cells are characterized by heightened Lyn kinase activity and dysregulated autophagy.• Regulation of protein turnover by autophagy plays a key role in erythropoiesis and red cell integrity.Chorea-acanthocytosis is one of the hereditary neurodegenerative disorders known as the neuroacanthocytoses. Chorea-acanthocytosis is characterized by circulating acanthocytes deficient in chorein, a protein of unknown function. We report here for the first time that chorea-acanthocytosis red cells are characterized by impaired autophagy, with cytoplasmic accumulation of active Lyn and of autophagy-related proteins Ulk1 and Atg7. In chorea-acanthocytosis erythrocytes, active Lyn is sequestered by HSP90-70 to form high-molecular-weight complexes that stabilize and protect Lyn from its proteasomal degradation, contributing to toxic Lyn accumulation. An interplay between accumulation of active Lyn and autophagy was found in chorea-acanthocytosis based on Lyn coimmunoprecipitation with Ulk1 and Atg7 and on the presence of Ulk1 in Lyncontaining high-molecular-weight complexes. In addition, chorein associated with Atg7 in healthy but not in chorea-acanthocytosis erythrocytes. Electron microscopy detected multivesicular bodies and membrane remnants only in circulating chorea-acanthocytosis red cells. In addition, reticulocyte-enriched chorea-acanthocytosis red cell fractions exhibited delayed clearance of mitochondria and lysosomes, further supporting the impairment of authophagic flux. Because autophagy is also important in erythropoiesis, we studied in vitro CD341 -derived erythroid precursors. In chorea-acanthocytosis, we found (1) dyserythropoiesis; (2) increased active Lyn; (3) accumulation of a marker of autophagic flux and autolysososme degradation; (4) accumlation of Lamp1, a lysosmal membrane protein, and LAMP1-positive aggregates; and (5) reduced clearance of lysosomes and mitochondria. Our results uncover in choreaacanthocytosis erythroid cells an association between accumulation of active Lyn and impaired autophagy, suggesting a link between chorein and autophagic vesicle trafficking in erythroid maturation. (Blood. 2016;128(25):2976-2987

show abstract

“…C57BL/6 Hx -/-mice and Hbb th3/+ mice as a model of β-thalassemia were described previously [20,[25][26][27][28][29]. All mice were housed in our animal facility, with a 12-h dark/light cycle and access to standard laboratory chow and tap water ad libitum.…”

Section: Mice and Treatmentsmentioning

confidence: 99%

Hemopexin counteracts systolic dysfunction induced by heme-driven oxidative stress

Ingoglia

Sag

Rex

et al. 2017

Free Radical Biology and Medicine

Self Cite

View full text Add to dashboard Cite

Heart failure is a leading cause of morbidity and mortality in patients affected by different disorders associated to intravascular hemolysis. The leading factor is the presence of pathologic amount of pro-oxidant free heme in the bloodstream, due to the exhaustion of the natural heme scavenger Hemopexin (Hx). Here, we evaluated whether free heme directly affects cardiac function, and tested the therapeutic potential of replenishing serum Hx for increasing serum heme buffering capacity.The effect of heme on cardiac function was assessed in vitro, on primary cardiomyocytes and H9c2 myoblast cell line, and in vivo, in Hx -/-mice and in genetic and acquired mouse models of intravascular hemolysis. Purified Hx or anti-oxidants N-Acetyl-L-cysteine and α-tocopherol were used to counteract heme cardiotoxicity.In mice, Hx loss/depletion resulted in heme accumulation and enhanced reactive oxygen species (ROS) production in the heart, which ultimately led to severe systolic dysfunction. Similarly, high ROS reduced systolic Ca 2+ transient amplitudes and fractional shortening in primary cardiomyocytes exposed to free heme. In keeping with these Ca 2+ handling alterations, oxidation and CaMKIIdependent phosphorylation of Ryanodine Receptor 2 were higher in Hx -/-hearts than in controls.Administration of anti-oxidants prevented systolic failure both in vitro and in vivo. Intriguingly, Hx rescued contraction defects of heme-treated cardiomyocytes and preserved cardiac function in hemolytic mice.We show that heme-mediated oxidative stress perturbs cardiac Ca 2+ homeostasis and promotes contractile dysfunction. Scavenging heme, Hx counteracts cardiac heme toxicity and preserves left ventricular function. Our data generate the rationale to consider the therapeutic use of Hx to limit the cardiotoxicity of free heme in hemolytic disorders.

show abstract

Membrane association of peroxiredoxin-2 in red cells is mediated by the N-terminal cytoplasmic domain of band 3

Cited by 75 publications

References 44 publications

Cysteine Oxidation Targets Peroxiredoxins 1 and 2 for Exosomal Release through a Novel Mechanism of Redox-Dependent Secretion

Cysteine Oxidation Targets Peroxiredoxins 1 and 2 for Exosomal Release through a Novel Mechanism of Redox-Dependent Secretion

A new molecular link between defective autophagy and erythroid abnormalities in chorea-acanthocytosis

Hemopexin counteracts systolic dysfunction induced by heme-driven oxidative stress

Contact Info

Product

Resources

About