Verotoxin (Shiga Toxin) Sensitizes Renal Epithelial Cells to Increased Heme Toxicity

Bitzan, Martin; Bickford, Brandi B.; Foster, Gregory H.

doi:10.1097/01.asn.0000138547.51867.43

Cited by 31 publications

(24 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hemin induces oxidative stress in endothelial cells [2,18,33,34]. On the one hand, hemin-induced oxidative stress may stimulate apoptosis of nucleated cells [7,47]; on the other hand, it upregulates heme oxidase [2,15,18,30], which in turn confers resistance to apoptosis [2,30,66]. Heme oxidase further stimulates an inflammatory response [73], which may by augmented by Hemin-induced formation of Egr-1 [31].…”

Section: Discussionmentioning

confidence: 99%

Hemin-induced suicidal erythrocyte death

2009

View full text Add to dashboard Cite

Several diseases, such as malaria, sickle cell disease, and ischemia/reperfusion may cause excessive formation of hemin, which may in turn trigger hemolysis. A variety of drugs and diseases leading to hemolysis triggers suicidal erythrocyte death or eryptosis, i.e., cell membrane scrambling and cell shrinkage. Eryptosis is elicited by increased cytosolic Ca 2+ activity and by ceramide. The present study explored whether hemin stimulates eryptosis. Cell membrane scrambling was estimated from annexin Vbinding to phosphatidylserine exposed at the cell surface, cell shrinkage from forward scatter in fluorescence-activated cell sorter analysis, cytosolic Ca 2+ activity from Fluo3 fluorescence and ceramide formation from fluorescencelabeled antibody binding. Exposure to hemin (1-10 μM) within 48 h significantly increased annexin V-binding, decreased forward scatter, increased cytosolic Ca 2+ activity, and stimulated ceramide formation. In conclusion, hemin stimulates suicidal cell death, which may in turn contribute to the clearance of circulating erythrocytes and thus to anemia.

show abstract

Section: Discussionmentioning

confidence: 99%

Hemin-induced suicidal erythrocyte death

2009

View full text Add to dashboard Cite

show abstract

“…Infections with Shiga toxin producing Escherichia coli may lead to haemolytic uremic syndrome (HUS) [1,2,3,4], a disorder characterized by haemolytic anaemia with fragmented erythrocytes, thrombocytopenia and acute renal failure [2,5,6,7,8,9,10]. Escherichia coli may produce Shiga toxins 1 and/or 2 (Vero toxins or Vero cytotoxins) [2,11].…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of Renal Klotho Expression by Shiga Toxin 2

Feger¹,

Mia²,

Pakladok³

et al. 2014

Kidney Blood Press Res

View full text Add to dashboard Cite

Background/Aims: Shiga toxin 2 may trigger classical hemolytic uremic syndrome (HUS) eventually leading to renal failure. Klotho, a transmembrane protein, protease and hormone mainly expressed in kidney is involved in the regulation of renal phosphate excretion and also retains renal protective effects. Renal failure is associated with renal depletion of klotho. The present study explored the influence of Shiga toxin 2 on renal klotho expression. Methods: Mice were injected with either solvent or Shiga toxin 2 and urinary flow rate and phosphate excretion were determined in metabolic cages. Renal transcript levels were measured by quantitative RT-PCR and renal protein abundance by Western blotting. Plasma concentrations of 1,25(OH)₂D₃ and FGF23 were determined by ELISA and plasma phosphate and urea concentrations by photometry. Results: Shiga toxin 2 treatment was followed by increase of plasma urea concentration, urinary flow rate and renal phosphate excretion but not of plasma phosphate concentration. Shiga toxin 2 treatment strongly decreased klotho mRNA expression and klotho protein abundance in renal tissue. Shiga toxin 2 treatment further increased tumor necrosis factor (TnfE) mRNA levels, as well as protein abundance of phosphorylated p38 MAPK in renal tissue. The treatment significantly increased renal Cyp27b1 and decreased renal Cyp24a1 mRNA levels without significantly altering plasma 1,25(OH)₂D₃ levels. Shiga toxin 2 treatment was further followed by increase of plasma FGF23 concentrations. Conclusion: Shiga toxin 2 treatment stimulated TnfE transcription, down-regulated renal klotho expression and increased FGF23 formation, effects presumably contributing to renal tissue injury. i 2015 S. Karger AG, Basel

show abstract

“…The ability of Shiga toxins to interact with different cell types seems to play a role in the development of disease, and the finding that Shiga toxins bind to activated blood platelets [69] may be important for the pathogenesis of HUS. However, the symptoms seen in connection with HUS can be caused by a combination of Shiga toxin-induced effects [70][71][72][73][74][75][76].…”

Section: Binding Of Toxins To Cell Surface Receptorsmentioning

confidence: 99%