Faculty of Food Technology and Biotechnology, University of Zagreb
Abstract
Urokinase plasminogen activator (uPA) and its inhibitors (PAI) are elements of plasminogen activation system, a proteolytic system involved in many physiological and patological processes. In this paper their induction by etoposide, a topoisomerase II inhibitor, in A1235 glioblastoma cell strain is described. Etoposide induced uPA and PAI production, in a dose- and time-dependent manner. Induction was based on the activation of their promoters and extracellular proteolysis was dependent on their equilibrium. Etoposide caused p53 activation and p21 and gadd45 induction, which could be responsible for the cell growth arrest. Our data indicate that several pathways could be involved in the uPA and PAI induction.Urokinazni tip plazminogenskog aktivatora (uPA) i njegovi inhibitori (PAI) dijelovi su plazminogenskog aktivacijskog sustava, proteolitičkog sustava uključenog u mnoge fiziološke i patološke procese. U ovom je radu opisana njihova indukcija etopozidom, inhibitorom topoizomeraze II, u stanicama glioblastoma A1235. Etopozid je inducirao uPA i PAI ovisno o koncentraciji i vremenu inkubacije. Indukcija je ovisila o aktivaciji njihova promotora, a ekstracelularna proteoliza o njihovoj ravnoteži. Etopozid je uzrokovao aktivaciju p53, kao i indukciju p21 i gadd45, te bi oni mogli biti odgovorni za zaustavljanje staničnog rasta. Rezultati upućuju da bi nekoliko signalnih puteva moglo sudjelovati u indukciji uPA i PAI
