Ana Lina Vodusek, Katja Goricar, Barbara Gazic, Vita Dolzan and Janez Jazbec
through lipid peroxidation, protein modification, membrane disruption and mitochondrial damage. 11 , 12
The thyroid cell is constantly exposed to ROS and an imbalance between pro- and anti-oxidative factors has been suggested as an important mechanism in thyroid carcinogenesis. The accumulation of oxidative DNA damage may drive genomic instability events and lead to somatic mutations. Many studies have shown that oxidants are increased and antioxidants are decreased in patients with thyroid cancer. 13 - 19
The most important antioxidants in the thyroid are
Blaz Krhin, Katja Goricar, Barbara Gazic, Vita Dolzan and Nikola Besic
, complex defence mechanisms including many enzymes, proteins and antioxidants are involved. Antioxidant enzymes such as manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPX) and catalase (CAT) directly eliminate ROS, while glutathione-S-transferases (GSTs) detoxify cytotoxic secondary metabolites. Numerous functional polymorphisms in the genes coding for antioxidant enzymes have been described that may also modify their ROS detoxification capacity. 17
Oxidative stress and ROS have been associated with several cancers and also many complex diseases like
Background. Astroglial cells are frequently involved in malignant transformation. Besides apoptosis, necroptosis, a different form of regulated cell death, seems to be related with glioblastoma genesis, proliferation, angiogenesis and invasion. In the present work we elucidated mechanisms of necroptosis in cultured astrocytes, and compared them with apoptosis, caused by staurosporine.
Materials and methods. Cultured rat cortical astrocytes were used for a cell death studies. Cell death was induced by different concentrations of staurosporine, and modified by inhibitors of apoptosis (z-vad-fmk) and necroptosis (nec- 1). Different forms of a cell death were detected using flow cytometry.
Results. We showed that staurosporine, depending on concentration, induces both, apoptosis as well as necroptosis. Treatment with 10-7 M staurosporine increased apoptosis of astrocytes after the regeneration in a staurosporine free medium. When caspases were inhibited, apoptosis was attenuated, while necroptosis was slightly increased. Treatment with 10-6 M staurosporine induced necroptosis that occurred after the regeneration of astrocytes in a staurosporine free medium, as well as without regeneration period. Necroptosis was significantly attenuated by nec-1 which inhibits RIP1 kinase. On the other hand, the inhibition of caspases had no effect on necroptosis. Furthermore, staurosporine activated RIP1 kinase increased the production of reactive oxygen species, while an antioxidant BHA significantly attenuated necroptosis.
Conclusion. Staurosporine can induce apoptosis and/or necroptosis in cultured astrocytes via different signalling pathways. Distinction between different forms of cell death is crucial in the studies of therapy-induced necroptosis.
genotypic origin in bovine meat. J Sci Food Agr 2005; 85 : 629-32.
Arabshahi-D S, Devi V, Urooj A. Evaluation of antioxidant activity of some plant extracts and their heat, pH and storage stability. Food Chem 2007; 100 : 100-5.
Ndabigengesere A, Narasiah KS. Quality of water treated by coagulation using Moringa oleifera seeds. Water Res 1998; 32 : 781-91.
Ndabigengesere A, Narasiah KS, Talbot BG. Active agents and mechanism of coagulation of turbid waters using Moringa oleifera
Ivana Steiner, Nikolina Stojanovic, Aljosa Bolje, Anamaria Brozovic, Denis Polancec, Andreja Ambriovic-Ristov, Marijana Radic Stojkovic, Ivo Piantanida, Domagoj Eljuga, Janez Kosmrlj and Maja Osmak
, USA) was added in wells. Experiment was repeated at least three times.
For determination of colony formation 1000 cells were seeded in 6 cm dish. The next day the cells were pretreated either with 5 mM NAC or with 1 mM (HEp-2 cells) or 0.125 mM (H460 cells) tempol. Two hours later different concentrations of 2b were added in dishes with or without ROS scavengers. The effect of antioxidants on colony formation alone was determined as well. After ten days of continuous treatment, the colonies were washed with PBS, fixed with methanol
Metka Filipič, Bojana Žegura, Bojan Sedmak, Irena Horvat-Žnidaršic, Aleksandra Milutinovič and Dušan Šuput
Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988; 175 : 184-91.
Milutinović A, Živin M, Zorc-Pleskovič R, Sedmak B, Šuput D. Nephrotoxic effects of chronic administration of microcystins -LR and -YR. Toxicon 2003; 42 : 281-8.
Moreno I, Pichardo S, Jos A, Gomez-Amores L, Mate A, Vazquez CM, Camean AM. Antioxidant enzyme activity and lipid peroxidation in liver and kidney of rats exposed to microcystin-LR administered
Roxana Buzas, Alexandru Florin Rogobete, Sonia Elena Popovici, Tudor Mateescu, Teodora Hoinoiu, Virgiliu-Bogdan Sorop, Tiberiu Bratu, Marian Ticlea, Calin Marius Popoiu and Dorel Sandesc
antioxidant therapy in traumatic spinal cord injuries. Rom J Anaesth Intensive Care. 2014;21:123-129.
17. Bedreag OH, Rogobete AF, Sarandan M, et al. Oxidative stress in severe pulmonary trauma in critical ill patients. Antioxidant therapy in patients with multiple trauma – a review. Anaesthesiol Intensive Ther. 2015;47:351-359. doi: 10.5603/AIT.a2015.0030.
18. Bedreag OH, Sandesc D, Chiriac SD, et al. The Use of Circulating miRNAs as Biomarkers for Oxidative Stress in Critically Ill Polytrauma Patients. Clin Lab. 2016;62:263-274. doi: 10.7754/Clin.Lab.2015
Alenka Franko, Nika Kotnik, Katja Goricar, Viljem Kovac, Metoda Dodic-Fikfak and Vita Dolzan
free radicals. The most frequently studied single nucleotide polymorphism (SNP), rs1800566, results in C to T change (c.609C>T), which causes proline to serine substitution (p.Pro187Ser). 21 Some studies found this polymorphism to be associated with an increased risk of several malignant diseases: lung cancer, colorectal cancer, breast cancer and bladder cancer. 22 , 23
Only few studies have investigated the interplay between asbestos exposure and genetic variability in antioxidant defence system in MM so far. 24 , 25 , 26 Nevertheless, the interaction between
Zhitong Bing, Guanghui Yang, Yanan Zhang, Fengling Wang, Caiyong Ye, Jintu Sun, Guangming Zhou and Lei Yang
, Gerisch B, Heeren G, Struys E, et al. Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J Biol 2007; 6: 10.
38. G rant C. Metabolic reconfiguration is a regulated response to oxidative stress. J Biol 2008; 7: 1.
39. S riharshan A, Boldt K, Sarioglu H, Barjaktarovic Z, Azimzadeh O, Hieber L, et al. Proteomic analysis by SILAC and 2D-DIGE reveals radiation-induced endothelial response: Four key pathways. J Proteomics 2012; 75: 2319-30.
40. S attler UGA, Mueller-Klieser W. The anti-oxidant
Janez Simenc, Damijana Mojca Juric and Metoda Lipnik-Stangelj
of VAS2870 could not be excluded and require further investigation.
The programmed cell death, in particular necroptosis, is executed through increased generation of ROS in several cell types, 19 , 31 including rat astrocytes. 23 Since VAS2870 operates as a powerful inhibitor of ROS generation, we explored the influence of VAS2870 on ROS production. Indeed, as shown in Figure 3E , VAS2870 significantly reduced ROS production at concentrations where probably does not act as an antioxidant. 30 However, in the untreated control cells, some basic level of ROS