Suppression by carotenoids of microtenoids of microcystin-induced morphological changes in mouse hepatocytes |
| |
Authors: | Rie Matsushima-Nishiwaki Yoshihiro Shidoji Shinji Nishiwaki Tetsuya Yamada Hisataka Moriwaki Yasutoshi Muto |
| |
Affiliation: | (1) Second Department of Pathology, Gifu University School of Medicine, 500 Gifu, Japan;(2) First Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, 500 Gifu, Japan |
| |
Abstract: | Microcystin-LR is a liver tumor promoter in the okadaic acid class, a group of potent inhibitors of protein phosphatases 1
and 2A. Because of inhibition of protein phosphatases, microcystin-LR induces hyperphosphorylation of cellular proteins, including
cytoskeletal proteins—cytokeratins 8 and 18—and causes morphological changes in mouse hepatocytes in primary culture. We studied
the effects of carotenoids to antagonize microcystin-LR-induced morphological changes in hepatocytes. β-Carotene (100 nM to
100 μM), suppressed the morphological changes induced by 100 nM microcystin-LR in a dose-dependent manner. Other carotenoids
tested exerted similar suppressive effects, although retinoids, such as all-trans retinol, all-trans retinoic acid, and 9-cis retinoic acid, were only weakly suppressive. The relative potency of the suppression correlated significantly with the number
of conjugated double bonds in thetrans configuration. β-Carotene strongly suppressed the hyperphosphorylation of cellular proteins induced by microcystin-LR without
significant changes in the basal phosphorylation level. Other antioxidants, such as α-tocopherol, did not protect the cells
against microcystin-LR. Taken together, the antagonistic effects of carotenoids against microcystin-LR are difficult to explain
by their antioxidant or provitamin A activities. Suppression of the hyperphosphorylation of cellular proteins may be a novel
mechanism by which carotenoids inhibit tumor promotion. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|