The effects of teleocidin and aplysiatoxin tumor promoters on epithelial tight junctions and transepithelial permeability: comparison to phorbol esters.
Control of transepithelial permeability by regulation of tight junctions is exerted by the non-phorbol ester tumor promoters, teleocidin and aplysiatoxin. Similar to the phorbol esters, tetradecanoylphorbol-13-acetate (TPA) and phorbol dibutyrate (PDBU), both teleocidin and aplysiatoxin cause a reversible decrease of transepithelial voltage and transepithelial resistance across LLC-PK1 renal epithelial cell sheets at concentrations as low as 10(-8) M. These compounds are effective from either side of these polar epithelial cells, i.e. apical or basolateral. The decreases in transepithelial gradients and resistance are paralleled by a rise in the transepithelial (paracellular) flux of D-mannitol between the cells (through the tight junctions). These four tumor promoters, TPA, PDBU, teleocidin and aplysiatoxin, are all known protein kinase C activators, and support the case for protein-kinase-C-mediated control of tight junctional permeability.
Mullin
J M
JM
Lankenau Medical Research Center, Philadelphia, PA.
McGinn
M T
MT
Snock
K V
KV
Imaizumi
S
S
D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology; D008235:Lyngbya Toxins / Q000494:pharmacology*; D010539:Permeability; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D008235:Lyngbya Toxins; C022176:teleocidins; D015240:Phorbol 12,13-Dibutyrate; C006610:aplysiatoxin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate