Mechanism of induced resistance to protein inhibitors of proliferation.
A 12 kD protein (IHP-12) was isolated from the cytosol of liver cells; IHP-12 inhibited proliferation of the liver cells by 50% when injected at 2.5 mg/100 g animal weight. Repeated injections of IHP-12 induced resistance of the liver cells to its anti-proliferative effect. After intraperitoneal injection, IHP-12 is localized in the cytosol and to a lesser extent, in cell nuclei. IHP-12 is degraded in the cytosol but in nuclei it retained its native structure for at least 8 h. The mechanism of induced resistance to IHP-12 was not related to a change in cell binding of IHP-12, its distribution in cellular compartments, and intracellular metabolism. The induced resistance may be associated with a change in the direction of IHP-12 activity, i.e., change in its function in the animal.
Bozhkov
A I
AI
Institute of Biology, Kharkov State University, Ukraine. bozhkov@geron.kharkov.ua
Shevtsova MYa
Malyshev
A B
AB
Shentseva
E A
EA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004351:Drug Resistance; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D008115:Liver Regeneration; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D006131:Growth Inhibitors; D011506:Proteins; D012313:RNA; D004247:DNA