Alteration of α-spectrin ubiquitination after hemorrhagic shock

Caprio, Kimberly; Condon, Michael R.; Deitch, E. A.; Xu, D.; Feketova, Eleonora; Machiedo, George W.

doi:10.1016/j.amjsurg.2008.07.019

Cited by 8 publications

(9 citation statements)

References 20 publications

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“…By comparison, in a 4.5 h animal model of trauma (T) and hemorrhagic shock (HS), where rats underwent a laparotomy followed by 90 hemorrhagic shock (T/HS, mean arterial pressure 30–35 mmHg) Caprio et al [ 132 ] reported that T/HS compared to trauma without hemorrhagic shock, altered RBC morphology (echinocyte and spheroechinocyte formation) and rheology (decreased RBC deformability). While no change in RBC membrane protein (α,β-spectrin, ankyrin, band 3, protein 4.1/4.2, protein 4.9 and actin) content was detected, serine phosphorylation increased in β-spectrin and ubiquitination decreased in α-spectrin.…”

Section: Alterations In Rbc Membrane Proteins In Critically Ill Pamentioning

confidence: 99%

The Effect of Sepsis on the Erythrocyte

Bateman

Sharpe

Singer

et al. 2017

IJMS

137

131

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Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin’s affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O2-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

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Section: Alterations In Rbc Membrane Proteins In Critically Ill Pamentioning

confidence: 99%

The Effect of Sepsis on the Erythrocyte

Bateman

Sharpe

Singer

et al. 2017

IJMS

137

131

View full text Add to dashboard Cite

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“…In addition, we have recently shown that the loss of RBC deformability is associated with decreased alpha-spectrin ubiquitination of the RBC membrane. 12 Although preventing mesenteric lymph from reaching the systemic circulation by ligating the mesenteric lymph duct prevents T/HS-induced RBC deformability and shape changes, it remains unclear whether T/HS lymph itself is sufficient to induce RBC injury or requires the activation of other factors during the T/HS period to exert its effect. Therefore, we tested the hypothesis that whether gut-derived factors carried in T/HS lymph is sufficient to induce RBC injury by infusing T/HS lymph into normal rats and measuring RBC deformability.…”

mentioning

confidence: 99%

Intravenous Injection of Mesenteric Lymph Produced During Hemorrhagic Shock Decreases RBC Deformability in the Rat

Condon

Senthil

et al. 2011

Journal of Trauma: Injury, Infection &Amp; Critical Care

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Objective To test the hypothesis that gut-derived factors carried in trauma-hemorrhagic shock (T/HS) lymph are sufficient to induce red blood cells (RBC) injury, to investigate their potential mechanisms of action, and to define the time post-T/HS that these factors appear in the lymph. Methods Mesenteric lymph collected from T/HS or trauma-sham shock (T/SS) rats over different time periods was injected intravenously into male rats at a rate of 1 mL/h for 3 hours. RBC deformability was measured using laser-assisted ektacytometer to calculate the elongation index. From the shear-stress elongation curve, the stress required for the erythrocytes to reach 50% of their maximal elongation was also determined. RBC deformability was measured before lymph infusion and at 1 hour and 3 hours after the initiation of lymph infusion. The effect of the lymph samples (5% v/v) was also determined in vitro by incubating naïve whole blood with the lymph samples. The potential role of T/HS lymph-induced RBC oxidant injury mediated by inducible nitric oxide synthase (iNOS)-generated oxidants and/or white blood cells (WBC) was investigated using iNOS inhibitors and WBC depletion, respectively. In all the in vivo studies, five to seven rats were studied per group. Results The intravenous injection of T/HS lymph but not T/SS lymph caused in vivo RBC injury. The biological activity of T/HS lymph varied over time with the RBC-injurious factors being produced only during the first 3 hours postshock. The in vivo inhibition of iNOS did not prevent lymph-induced RBC injury. T/HS lymph incubated in vitro with naïve whole blood resulted in RBC injury, but this injury was not observed in blood depleted of WBC. Conclusions These results indicate that T/HS lymph produced during the initial 3-hour postshock period is sufficient to induce RBC injury in otherwise normal rats and that the lymph-induced RBC injury is not dependent on activation of the iNOS pathway but seems to require WBC.

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“…183 Caprio et al have found that diminished spectrin ubiquitination is also the basis for RBC rigidity in multiple organ dysfunction syndrome (MODS). 196 As explained in our previous reviews, and shown in Figure 7, there is every reason to believe that aSpII has the same chimeric E2/E3 activity as aSpI. 8,9 As this has been previously reviewed, we will focus on the reasons demonstrated by Figure 7.…”

Section: Extracellular Cell -Cell Interactionsmentioning

confidence: 98%

The Spectrinome: The Interactome of a Scaffold Protein Creating Nuclear and Cytoplasmic Connectivity and Function

Goodman

Johnson

Youngentob

et al. 2019

Exp Biol Med (Maywood)

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We provide a review of Spectrin isoform function in the cytoplasm, the nucleus, the cell surface, and in intracellular signaling. We then discuss the importance of Spectrin’s E2/E3 chimeric ubiquitin conjugating and ligating activity in maintaining cellular homeostasis. Finally we present spectrin isoform subunit specific human diseases. We have created the Spectrinome, from the Human Proteome, Human Reactome and Human Atlas data and demonstrated how it can be a useful tool in visualizing and understanding spectrins myriad of cellular functions. Impact statement Spectrin was for the first 12 years after its discovery thought to be found only in erythrocytes. In 1981, Goodman and colleagues 1 found that spectrin-like molecules were ubiquitously found in non-erythroid cells leading to a great multitude of publications over the next thirty eight years. The discovery of multiple spectrin isoforms found associated with every cellular compartment, and representing 2-3% of cellular protein, has brought us to today’s understanding that spectrin is a scaffolding protein, with its own E2/E3 chimeric ubiquitin conjugating ligating activity that is involved in virtually every cellular function. We cover the history, localized functions of spectrin isoforms, human diseases caused by mutations, and provide the spectrinome: a useful tool for understanding the myriad of functions for one of the most important proteins in all eukaryotic cells.

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Alteration of α-spectrin ubiquitination after hemorrhagic shock

Cited by 8 publications

References 20 publications

The Effect of Sepsis on the Erythrocyte

The Effect of Sepsis on the Erythrocyte

Intravenous Injection of Mesenteric Lymph Produced During Hemorrhagic Shock Decreases RBC Deformability in the Rat

The Spectrinome: The Interactome of a Scaffold Protein Creating Nuclear and Cytoplasmic Connectivity and Function

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