Clostridium perfringens α-Toxin Activates the Sphingomyelin Metabolism System in Sheep Erythrocytes

Ochi, Sadayuki; Oda, Masataka; Matsuda, Hisaaki; Ikari, Syusuke; Sakùrai, Jun

doi:10.1074/jbc.m307046200

Cited by 68 publications

(55 citation statements)

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“…We have also demonstrated that the alpha-toxin-induced hemolysis of sheep erythrocytes is dependent on the activation of the sphingomyelin metabolic system through GTP-binding proteins, especially the formation of sphingosine 1-phosphate [22,23].Therefore, the toxin-induced activation of phospholipid metabolism through G protein is closely involved in the biological activities. In the present review, we demonstrate the relationship between phospholipid metabolism via G protein and the biological activities induced by alpha-toxin.…”

Section: Introductionmentioning

confidence: 92%

“…Sheep erythrocytes contain large amounts of sphingomyelin (SM) but not PC. Alpha-toxin simultaneously induced hemolysis and a reduction in the levels of SM in the membrane and an increase in ceramide and sphingosine 1-phosphate (S1P) [22]. It seemed that the toxin-induced hemolysis of sheep erythrocytes is closely related to the hydrolysis of SM in the membrane by the SMase activity of alpha-toxin.…”

Section: Activation Of Sphingomyelin Metabolism Through Gtpbinding Prmentioning

confidence: 99%

“…These observations indicate that S1P plays an intracellular role in the toxin-induced hemolysis, not an extracellular one, suggesting that it functions as a second messenger in the process. S1P itself caused no hemolysis of saponin-permeabilized cells, suggesting that hemolysis may be induced by a combination of S1P and other events elicited by the toxin in the cells [22] (Figure 3). GTP[γS] stimulated alpha-toxin-induced hemolysis, hydrolysis of SM, and formation of S1P in sheep erythrocytes.…”

Section: Activation Of Sphingomyelin Metabolism Through Gtpbinding Prmentioning

confidence: 99%

“…However, a markedly lower level of sphingosine, compared with S1P, was detected, although S1P increased with an increase in the dose of the toxin. It therefore is likely that sphingosine is rapidly metabolized to S1P in the cells treated with the toxin [22]. N-Oleoylethanolamine, a ceramidase inhibitor, inhibited the toxin-induced hemolysis and caused ceramide to accumulate in the toxin-treated cells.…”

Section: Activation Of Sphingomyelin Metabolism Through Gtpbinding Prmentioning

confidence: 99%

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Role of Phospholipid Metabolism and G Protein in the Action Induced by Clostridium Perfringens Alpha-Toxin

Nagahama¹,

Oda²,

Ochi³

et al. 2012

J Glycom Lipidom

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Section: Introductionmentioning

confidence: 92%

Section: Activation Of Sphingomyelin Metabolism Through Gtpbinding Prmentioning

confidence: 99%

Section: Activation Of Sphingomyelin Metabolism Through Gtpbinding Prmentioning

confidence: 99%

Section: Activation Of Sphingomyelin Metabolism Through Gtpbinding Prmentioning

confidence: 99%

See 2 more Smart Citations

Role of Phospholipid Metabolism and G Protein in the Action Induced by Clostridium Perfringens Alpha-Toxin

Nagahama¹,

Oda²,

Ochi³

et al. 2012

J Glycom Lipidom

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“…SMase Activity Assay-The hemolytic activity of the enzyme was determined by the amount of hemoglobin released from sheep erythrocytes using a method described previously (17). The reaction mixture containing the enzyme at various concentrations, 3% (w/v) sheep erythrocytes, 20 mM Tris-HCl buffer (pH 7.5), 3 mM MgCl 2 , and 0.9% (w/v) NaCl, was incubated for 30 min at 37°C and then centrifuged at 500 ϫ g for 3 min in order to prepare the test aliquot.…”

Section: Methodsmentioning

confidence: 99%

Structural Basis of the Sphingomyelin Phosphodiesterase Activity in Neutral Sphingomyelinase from Bacillus cereus

Ago

Oda²,

Takahashi³

et al. 2006

Journal of Biological Chemistry

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Sphingomyelinase (SMase) from Bacillus cereus (Bc-SMase) hydrolyzes sphingomyelin to phosphocholine and ceramide in a divalent metal ion-dependent manner. Bc-SMase is a homologue of mammalian neutral SMase (nSMase) and mimics the actions of the endogenous mammalian nSMase in causing differentiation, development, aging, and apoptosis. Thus Bc-SMase may be a good model for the poorly characterized mammalian nSMase. The 2؉ or Co 2؉ may provide a common structural framework applicable to phosphohydrolases belonging to the DNase I-like folding superfamily. In addition, the structural features and site-directed mutagenesis suggest that the specific ␤-hairpin with the aromatic amino acid residues participates in binding to the membrane-bound sphingomyelin substrate.Sphingomyelinase (SMase, 4 EC 3.1.4.12) from Bacillus cereus (BcSMase) exhibits both phospholipase C activity, hydrolyzing sphingomyelin (SM) to phosphocholine and ceramide, and hemolytic activity. Both Bc-SMase activities occur in a divalent metal ion-dependent manner (1-3). Bc-SMase requires Mg 2ϩ for sphingomyelin hydrolytic activity and an additional Ca 2ϩ for hemolytic activity (1-6). Mutagenesis studies have shown that Glu-53 is the essential Mg 2ϩ -binding amino acid (5).The catalytic mechanism of the sphingomyelin hydrolytic activity remains to be elucidated in atomic detail, as there are no crystal structures of SMase in complex with the essential divalent metal ions. The sphingomyelin hydrolytic activity of Bc-SMase is believed to proceed in the manner of acid base catalysis, in which His-296 is proposed to generate an activated water and the essential Mg 2ϩ ion at Glu-53 is suggested to stabilize a negatively charged transition state. The proposed catalytic mechanism of Bc-SMase is similar to that of bovine DNase I. In fact, Bc-SMase and bovine DNase I are homologous proteins and share a common architecture of conserved putative catalytic amino acid residues (7). However, the proposed catalytic mechanism does not fully explain the role of the essential divalent metal ion, i.e. the divalent metal ion type dependence for hydrolytic catalysis, because of the lack of the bound essential metal ions in all the currently available structures.Bc-SMase and neutral sphingomyelinase (nSMase) in mammalian cells share similar metal ion dependence and considerable amino acid sequence identity (20%), including conserved residues involved in divalent metal ion binding, and are thus believed to have a similar hydrolytic mechanism. SMases in mammalian cells are classified into the following three groups according to the optimum pH of the SM hydrolytic activity: neutral SMase, acid SMase, and alkaline SMase (8). The detailed mechanism of the sphingomyelin hydrolysis activity of Bc-SMase may provide insight into sphingolipid metabolism in mammalian cells (9 -11).The only available structure of SMase is from the bacterium, Listeria ivanovii, reported recently (7). The bacterial SMase was confirmed to be a member of the DNase I-like folding superfamily (12)(13)(14)...

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Bacterial phospholipases C with dual activity: phosphatidylcholinesterase and sphingomyelinase

et al. 2021

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Bacterial phospholipases and sphingomyelinases are lipolytic esterases that are structurally and evolutionarily heterogeneous. These enzymes play crucial roles as virulence factors in several human and animal infectious diseases. Some bacterial phospholipases C (PLCs) have both phosphatidylcholinesterase and sphingomyelinase C activities. Among them, Listeria monocytogenes PlcB, Clostridium perfringens PLC, and Pseudomonas aeruginosa PlcH are the most deeply understood. In silico predictions of substrates docking with these three bacterial enzymes provide evidence that they interact with different substrates at the same active site. This review discusses structural aspects, substrate specificity, and the mechanism of action of those bacterial enzymes on target cells and animal infection models to shed light on their roles in pathogenesis.

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Clostridium perfringens α-Toxin Activates the Sphingomyelin Metabolism System in Sheep Erythrocytes

Cited by 68 publications

References 54 publications

Role of Phospholipid Metabolism and G Protein in the Action Induced by Clostridium Perfringens Alpha-Toxin

Role of Phospholipid Metabolism and G Protein in the Action Induced by Clostridium Perfringens Alpha-Toxin

Structural Basis of the Sphingomyelin Phosphodiesterase Activity in Neutral Sphingomyelinase from Bacillus cereus

Bacterial phospholipases C with dual activity: phosphatidylcholinesterase and sphingomyelinase

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