Phospholipase C from Clostridium perfringens stimulates acetyltransferase-dependent formation of platelet-activating factor in cultured intestinal epithelial cells (INT 407).
The mechanisms by which phospholipase C from Clostridium perfringens stimulates the formation of platelet-activating factor (PAF-acether) in cultured intestinal epithelial cells (INT 407) were investigated. Although stimulation with phospholipase C caused a significant formation of PAF-acether, there was no significant increase in the cellular levels of lysoPAF-acether after stimulation. Moreover, when cells prelabeled with 3H-1-O-alkyl-2-acyl-sn-glycerophosphocholine were stimulated with phospholipase C, the 3H-lysoPAF-acether content was not increased in stimulated cells as compared with unstimulated cells. When cells were preincubated with the calmodulin inhibitor trifluoperazine (TFPA), the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), or the combined phospholipase A2-inhibitor and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) before stimulation with phospholipase C, the PAF-acether formation was significantly decreased. The phospholipase A2 inhibitor 4-bromophenacyl bromide (BPB), on the other hand, had no significant effect on the PAF-acether formation. Preincubation with NDGA also decreased the levels of lysoPAF-acether, whereas BPB, H7, or TFPA had no such effect. These findings indicate that stimulation of acetyltransferase activity with increased acetylation of lysoPAF-acether may be one way by which phospholipase C from C. perfringens stimulates formation of PAF-acether in INT 407 cells.
Kald
B
B
Dept. of Occupational and Environmental Medicine, Faculty of Health Sciences, University of Linköping, Sweden.
Boll
R M
RM
Gustafson-Svärd
C
C
Sjödahl
R
R
Tagesson
C
C
D000123:Acetyltransferases / Q000502:physiology*; D002460:Cell Line; D003016:Clostridium perfringens / Q000201:enzymology*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D010738:Type C Phospholipases / Q000494:pharmacology*
D010972:Platelet Activating Factor; D000123:Acetyltransferases; D010738:Type C Phospholipases