Staphylococcus aureus alpha-toxin activates phospholipases and induces a Ca2+ influx in PC12 cells.
Staphylococcal alpha-toxin at subcytotoxic concentrations stimulated phosphatidylinositol turnover and arachidonic acid release in undifferentiated cultures of pheochromocytoma PC12 cells. Stimulation of phospholipase A2 but not C was dependent on extracellular calcium. Addition of staphylococcal alpha-toxin to PC12 cells caused a dose-dependent, biphasic increase in intracellular calcium measured by fura-2 fluorescence technique. Elevation of intracellular Ca2+ content occurred with a time course similar to those observed for stimulation of phospholipase A2. Alteration of membrane structure and formation of staphylococcal alpha-toxin pores facilitating an influx of Ca2+, represent the probable mechanisms by which phospholipases C and A2 are activated, respectively. These results suggest a possible involvement of Ca2+, phosphoinositides and arachidonic acid metabolites in the pathogenic action of staphylococcus alpha-toxin and caution against the general usage of this toxin as a permeabilizing agent to study stimulus-secretion coupling in secretory cells.
Fink
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Section on Growth Factors, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Contreras
M L
ML
Lelkes
P I
PI
Lazarovici
P
P
D000310:Adrenal Gland Neoplasms; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006460:Hemolysin Proteins / Q000494:pharmacology*; D010673:Pheochromocytoma; D010716:Phosphatidylinositols / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013211:Staphylococcus aureus; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D001095:Arachidonic Acids; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D010716:Phosphatidylinositols; C021091:staphylococcal alpha-toxin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D002118:Calcium