Relation between Serum Ubiquitin Levels and KT/V in Chronic Hemodialysis Patients

Akarsu, Ersin; Pirim, İbrahim; Selçuk, Nedim Yılmaz; Tombul, H.Z.; Çetinkaya, Ramazan

doi:10.1159/000046005

Cited by 18 publications

(14 citation statements)

References 5 publications

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“…Ub is a natural constituent of extracellular fluids, such as serum, plasma, or cerebrospinal fluid, and increased extracellular concentrations have been described in some diseases. 1,[7][8][9][10][11][12] However, no pathophysiologic role was attributed to extracellular Ub in these studies.…”

mentioning

confidence: 80%

Systemic Ubiquitin Release After Blunt Trauma and Burns: Association With Injury Severity, Posttraumatic Complications, and Survival

Majetschak

Zedler

Hostmann

et al. 2008

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

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mentioning

confidence: 80%

Systemic Ubiquitin Release After Blunt Trauma and Burns: Association With Injury Severity, Posttraumatic Complications, and Survival

Majetschak

Zedler

Hostmann

et al. 2008

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

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“…Elevated ubiquitin concentrations in biological fluids have been described in a variety of pathological conditions. [6][7][8][9][10][11][12] In vitro studies described effects of extracellular ubiquitin on apoptosis, growth regulation, microbial defence and cytokine production. [12][13][14][15] Recent in vivo studies showed pronounced anti-inflammatory effects in endotoxic and traumatic shock.…”

Section: Introductionmentioning

confidence: 99%

Targeting the monocytic ubiquitin system with extracellular ubiquitin

2006

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Summary Recent findings suggest that extracellular ubiquitin has pleiotropic effects on host defence mechanisms, but its cellular mechanism of action is not yet understood. Using fluorescence and in vivo confocal microscopy, we observed uptake of N-terminal fluorescein-labelled ubiquitin into human PBMC and MonoMac 6 cells. Immunoblotting experiments indicated that extracellular ubiquitin is then rapidly conjugated to a multitude of intracellular proteins. LPS and lipoteichoic acid significantly increased uptake and subsequent conjugation to intracellular proteins dose dependently. This mechanism showed saturation kinetics with a K d value for ubiquitin in the low nanomolar range (<10 nmol/L) and a B max value of 0.14-0.27 mmol ubiquitin/mg protein. These results suggest that the monocytic ubiquitin system can be targeted with physiologically relevant concentrations of extracellular ubiquitin during inflammation. This concept could provide a simple explanation for a multitude of extracellular ubiquitin's actions and open up new strategies to influence ubiquitin-dependent intracellular processes.

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“…[3][4][5][6] Furthermore, ubiquitin has also been detected in the extracellular space. Compared with the normal range, significantly increased ubiquitin levels have been described in serum or plasma during parasitic infections, 7 in alcoholic liver cirrhosis, 8 in type 2 diabetes, 9 in hairy cell leukemia, 10 and in patients with renal failure and hemodialysis treatment, 11,12 but data on the potential biologic functions of extracellular ubiquitin are rare. Besides possible lymphocyte-differentiating properties, extracellular ubiquitin has been reported to inhibit platelet activities 13 and IgG production in splenocyte cultures, 14 to synergistically effect lipopolysaccharide (endotoxin; LPS)-induced tumor necrosis factor-␣ (TNF-␣) production in a murine macrophage cell line, 15 and to be involved in growth regulation and induction of apoptosis in human hematopoietic cell lines.…”

Section: Introductionmentioning

confidence: 99%

Extracellular ubiquitin inhibits the TNF-α response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness

Majetschak

Krehmeier

Bardenheuer

et al. 2003

Blood

116

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Ubiquitin is suggested to play a key role in essential intracellular functions, such as heat shock response, protein breakdown, and regulation of immune responses. Ubiquitin has also been detected in the extracellular space, but the function and biologic significance is unclear. We describe a new function of extracellular ubiquitin and show that extracellular ubiquitin specifically inhibits ex vivo secretion of tumor necrosis factor-␣ (TNF-␣) and TNF-␣ mRNA expression from peripheral blood mononuclear cells (PBMNCs) in response to endotoxin in a dose-dependent manner. In contrast, the TNF-␣ response to zymosan or Staphylococcus aureus as well as the interleukin-6 (IL-6) and IL-8 responses to endotoxin were unaffected by ubiquitin. Measurement of serum ubiquitin levels showed a significant 5-to 7-fold increase in sepsis and trauma patients, to the level required for inhibition of the PBMNC TNF-␣ response to endotoxin by ubiquitin. Elevated ubiquitin levels in serum were significantly correlated with a reduced TNF-␣ production. Antibodies to ubiquitin were able to (1) significantly increase (2-to 5-fold) the TNF-␣ response to endotoxin in whole blood from trauma and sepsis patients, (2) completely neutralize the inhibitory effect of trauma patients' serum on healthy donors' TNF-␣ production, and (3) partially neutralize the inhibitory effect of sepsis patients' serum on healthy donors' TNF-␣ production. Ubiquitin-depleted serum from trauma patients lost the inhibitory activity for TNF-␣ production, whereas extracted endogenous ubiquitin exerts the inhibitory activity. The results demonstrate that extracellular ubiquitin acts as a cytokinelike protein with anti-inflammatory properties and indicate that extracellular ubiquitin is involved in the regulation of immunodepression in critical

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Relation between Serum Ubiquitin Levels and KT/V in Chronic Hemodialysis Patients

Cited by 18 publications

References 5 publications

Systemic Ubiquitin Release After Blunt Trauma and Burns: Association With Injury Severity, Posttraumatic Complications, and Survival

Systemic Ubiquitin Release After Blunt Trauma and Burns: Association With Injury Severity, Posttraumatic Complications, and Survival

Targeting the monocytic ubiquitin system with extracellular ubiquitin

Extracellular ubiquitin inhibits the TNF-α response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness

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