In vitro and in vivo effects of protein phosphatase inhibitors, microcystins and nodularin, on mouse skin and fibroblasts.
Three microcystins, YR, LR and RR and nodularin, all of which are hepatotoxic compounds, inhibited dose-dependently the activity of protein phosphatase 2A in and the specific [3H]okadaic acid binding to a cytosolic fraction of mouse skin, as strongly as okadaic acid. However, microcytins and nodularin did not induce any effects on mouse skin or primary human fibroblasts. Microinjection of microcystin YR into primary human fibroblasts induced morphological changes which were induced by incubation with okadaic acid. Microcystins and nodularin penetrate into the epithelial cells of mouse skin and human fibroblasts with difficulty, which reflects tissue specificity of the compounds.
Matsushima
R
R
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
Yoshizawa
S
S
Watanabe
M F
MF
Harada
K
K
Furusawa
M
M
Carmichael
W W
WW
Fujiki
H
H
D000818:Animals; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D004988:Ethers, Cyclic / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008387:Marine Toxins / Q000494:pharmacology*; D051379:Mice; D052998:Microcystins; D019319:Okadaic Acid; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010947:Plants, Toxic; D011485:Protein Binding; D054648:Protein Phosphatase 2; D012867:Skin / Q000201:enzymology*
D004988:Ethers, Cyclic; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C063998:nodularin; C065685:microcystin YR; D019319:Okadaic Acid; C063855:microcystin RR; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; C057862:cyanoginosin LR