caa a22 4500 445812680 CHVBK 20180317145216.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00411-010-0331-z doi (NATIONALLICENCE)springer-10.1007/s00411-010-0331-z Administration of rat acute-phase protein α2-macroglobulin before total-body irradiation initiates cytoprotective mechanisms in the liver [Elektronische Daten] [Desanka Bogojević, Goran Poznanović, Nevena Grdović, Ilijana Grigorov, Melita Vidaković, Svetlana Dinić, Mirjana Mihailović] Previously, we showed that administration of the acute-phase protein α2-macroglobulin (α2M) to rats before total-body irradiation with 6.7Gy (LD50/30) of X-rays provides the same level of radioprotection as amifostine. Here, we compare the cytoprotective effects of α2M and amifostine on rat liver. The potential of the liver to replenish cells destroyed by ionizing radiation was assessed by immunoblot analysis with antibody to proliferating cell nuclear antigen (PCNA). After irradiation, in unprotected rats PCNA decreased 6-fold from the basal level. In rats pretreated with either α2M or amifostine, PCNA was increased throughout a 4week follow-up period, indicating that hepatocyte proliferation was unaffected. Since PCNA is an important component of the repair machinery, its increased expression was accompanied by significantly lower DNA damage in α2M- and amifostine-treated rats. At 2weeks after irradiation, the Comet assay revealed a 15-fold increase in DNA damage in unprotected rats, while in α2M- and amifostine-treated rats we observed 3- and 4-fold rise in damage, respectively. The improved protection to DNA damage was supported by elevated activity of the antioxidant systems. Compared to untreated rats, pretreatments with α2M and amifostine led to similar increases in levels of the inflammatory cytokine IL-6 and the redox-sensitive transcription factor NFκB, promoting upregulation of MnSOD, the major component of the cell's antioxidant axis, and subsequent increases in Mn/CuZnSOD and catalase enzymatic activities. The results show that α2M induces protein factors whose interplay underlies radioprotection and support the idea that α2M is the central effector of natural radioprotection in the rat. Springer-Verlag, 2010 Bogojević Desanka Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut Poznanović Goran Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut Grdović Nevena Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut Grigorov Ilijana Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut Vidaković Melita Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut Dinić Svetlana Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut Mihailović Mirjana Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut Radiation and Environmental Biophysics Springer-Verlag 50/1(2011-03-01), 167-179 0301-634X 50:1<167 2011 50 411 https://doi.org/10.1007/s00411-010-0331-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00411-010-0331-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bogojević Desanka Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 700 1- Poznanović Goran Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 700 1- Grdović Nevena Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 700 1- Grigorov Ilijana Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 700 1- Vidaković Melita Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 700 1- Dinić Svetlana Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 700 1- Mihailović Mirjana Institute for Biological Research "Siniša Stanković”, University of Belgrade, Despot Stephen Blvd. 142, 11060, Belgrade, Serbia aut NATIONALLICENCE 773 0- Radiation and Environmental Biophysics Springer-Verlag 50/1(2011-03-01), 167-179 0301-634X 50:1<167 2011 50 411 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer