Abstract：
:Bolesatine, a glycoprotein from Boletus satanas Lenz, has previously been shown to be mitogenic to rat and human lymphocytes at very low concentrations, whereas higher concentrations inhibit protein synthesis in vitro and in several in vivo systems. The mechanism whereby this mitogenic activity occurs was previously unknown. To elucidate this mechanism, the effects of bolesatine have been studied in a cell-free system, VERO cells, and in vivo in rat thymus. In a cell-free system, bolesatine appears to be a direct effector of PKC. The activation is concentration dependent for 1-10 ng/ml. At the same time, VERO cells significantly proliferate when incubated with the bolesatine (3, 5 and 10 ng/ml), since the DNA synthesis increases by 27, 48, and 59%, for respectively, 3, 5 and 10 ng/ml compared with control. Moreover, Bolesatine (5 and 10 ng/ml) induces InsP3 release in a concentration-dependent manner (114 and 142%) as compared to control. In vivo, 24 h after oral administration of bolesatine to rates (20, 100 and 200 microg/kg), PKC activity is significantly increased in thymus. THe most effective doses (100 and 200 microg/kg) give 590-620% increase in cytosolic PKC activity and 85-91% increase in total PKC activity as compared to control. This PKC activation by bolesatine in rat thymus is directly linked to the mitogenic activity observed in vivo. Bolesatine is thus capable of activating the PKC directly and/or indirectly (via InsP3 release) during its mitogenic processes.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Ennamany R,Kretz O,Creppy EEdoi
10.1007/s002040050223subject
Has Abstractpub_date
1995-01-01 00:00:00pages
624-30issue
9eissn
0340-5761issn
1432-0738journal_volume
69pub_type
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