- Email: [email protected]
The effect of tocotrienols on high-fat diet-treated mice
S66
A. Stepanova et al. / Free Radical Biology and Medicine 120 (2018) S45–S166
P-70
Targeting CD44/xCT is a potential strategy to sensitize human neuroblastoma stem cells to etoposide Andrea Speciale 1, Barbara Marengo 1, Nicola Traverso 1, Claudia Cantoni 1, Silvia Ravera 2, Ombretta Garbarino 1, Maria Adelaide Pronzato 1, Cinzia Domenicotti 1 1 2
Department of Experimental Medicine, University of Genoa, Italy Department of Pharmacy, University of Genoa, Italy
Etoposide, commonly used to treat neuroblastoma (NB), acts by inducing pro-oxidant effects, but has limited efficacy due to NB cells becoming resistant by increasing glutathione (GSH) levels. Moreover, cancer stem cells (CSCs) expressing CD44, a PKC-alpha-modulated staminality marker, are able to influence GSH levels by stabilizing xCT, a transporter promoting the influx of cystine, essential for GSH synthesis. Therefore, CSCs derived from HTLA-230, a human NB cell line, and from etoposide– resistant HTLA (HTLA-ER) cells, were treated with etoposide alone or associated with sulfasalazine, an xCT inhibitor, or with a PKC-alpha inhibitor. In the CSCs originating from HTLA-ER cells, a 5-week treatment with sulfasalazine/PKC-alpha inhibitor plus etoposide reduced cell propagation and GSH levels, also promoting anaerobic glycolytic metabolism whereas in the CSCs originating from parental HTLA cells, similar effects were obtained already after 2 weeks of etoposide but the presence of sulfasalazine or PKC-alpha inhibitor did not change these results. Collectively, our data suggests that the modulation of CD44/xCT, by reducing GSH levels and favoring the anaerobic metabolic switch might be an effective strategy for inducing CSC death.
E-mail address: [email protected] Acknowledgements Grants from Genoa University
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.217
P-71
Treatment with a low concentration of ionomycin induced neurite degeneration via influx of calcium ions, mitochondrial-dependent superoxide production and mitochondrial membrane oxidations. These phenomena were recorded by a time-lapse live imaging system. Finally, these neurite degeneration prevented by antioxidant vita.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.218
P-72
The effect of tocotrienols on high-fat diet-treated mice Yugo Kato 1, Masashi Shirai 1, Yoshinori Aoki 2, Taisuke Koike 2, Koji Fukui 1 1
Molecular Cell Biology Laboratory, Department of Bioscience and Engineering, Shibaura Institute of Technology, Tokyo, Japan 2 Mitsubishi-chemical foods corporation, Japan
Obesity is increasing in developed countries and is well known to a risk factor of severe diseases such as diabetes and Alzheimer's disease. Several kinds of evidence have been demonstrated that these diseases relate to oxidative damage. However, the detailed mechanisms of it relation have not yet elucidated. Previously, we reported that cognitive dysfunction is induced in normal aged- and vitamin E (V.E)-deficient mice models via accumulation of brain oxidation. On the basis of these data, we hypothesized that obesity increased the risk of cognitive dysfunction via brain oxidation. Tocotrienols (T3s) which are one kind of vitamin E have many biological functions. The most famous function of T3s is antioxidant, and the function is stronger than that of tocopherols. Other beneficial function of T3s is neuroprotection and inhibitory effect of HMG-CoA reductase. In this study, we assessed motor and cognitive function of long- and short-term high-fat diettreated mice in the presence or absence of T3s. Furthermore, we measured V. E, TBARS and antioxidant enzyme activity in these mice liver, serum and brain. These results indicate that obesity induce cognitive dysfunction via brain oxidation and treatment with T3s may show anti-obesity and neuroprotective effect in our model.
E-mail address: [email protected]
Influx of calcium ions accelerates neurite degeneration via induction of microtubule destabilization
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.219
Koji Fukui, Saki Nakamura, Shunsuke Okihiro Molecular Cell Biology Laboratory, Department of Bioscience and Engineering, Shibaura Institute of Technology, Tokyo, Japan
Reactive oxygen species (ROS) attack several living organs and induce neuronal cell death. Previously, we found that treatment with a low concentration of hydrogen peroxide induced neurite degeneration prior to the cell death. The neurites showed abnormal morphologies including beads formation, shrinkage and fragmentation. This phenomenon also observed in hippocampus of the normal-aged and vitamin E-deficient mice. In order to clarify the mechanism of neurite degeneration, we measured lipid peroxidative products in hydrogen peroxide-treated cells. The LOOH levels were significantly increased compared to the untreated group. If cell membranes are oxidized by ROS, large parts of receptors and ion channels may be also damaged. Here, we show the elucidation of the relationship between calcium influx and neurite degeneration in cultured neurons. Treatment with an ionomycin (calcium ionophore) induced neuronal cell death in a concentration- and a time-dependent manner.
P-73
Neutrophils activation by carbon nanotubes functionalized with COOH-groups and conjugated with DNA Tatsiana Kulahava 1, Lena Golubewa 1, Nikita Vasilieu 1, Olesya Paddubskaya 2, Mikhail Shuba 2 1 Department of Biophysics, Physics Faculty, Belarusian State University, Minsk, Belarus 2 Research Institute for Nuclear Problems, Belarusian State University, Minsk, Belarus
Interaction of neutrophils with carbon nanotubes (CNT), 100–400 nm in length, functionalized with -COOH groups and non-covalently
A. Stepanova et al. / Free Radical Biology and Medicine 120 (2018) S45–S166
P-70
Targeting CD44/xCT is a potential strategy to sensitize human neuroblastoma stem cells to etoposide Andrea Speciale 1, Barbara Marengo 1, Nicola Traverso 1, Claudia Cantoni 1, Silvia Ravera 2, Ombretta Garbarino 1, Maria Adelaide Pronzato 1, Cinzia Domenicotti 1 1 2
Department of Experimental Medicine, University of Genoa, Italy Department of Pharmacy, University of Genoa, Italy
Etoposide, commonly used to treat neuroblastoma (NB), acts by inducing pro-oxidant effects, but has limited efficacy due to NB cells becoming resistant by increasing glutathione (GSH) levels. Moreover, cancer stem cells (CSCs) expressing CD44, a PKC-alpha-modulated staminality marker, are able to influence GSH levels by stabilizing xCT, a transporter promoting the influx of cystine, essential for GSH synthesis. Therefore, CSCs derived from HTLA-230, a human NB cell line, and from etoposide– resistant HTLA (HTLA-ER) cells, were treated with etoposide alone or associated with sulfasalazine, an xCT inhibitor, or with a PKC-alpha inhibitor. In the CSCs originating from HTLA-ER cells, a 5-week treatment with sulfasalazine/PKC-alpha inhibitor plus etoposide reduced cell propagation and GSH levels, also promoting anaerobic glycolytic metabolism whereas in the CSCs originating from parental HTLA cells, similar effects were obtained already after 2 weeks of etoposide but the presence of sulfasalazine or PKC-alpha inhibitor did not change these results. Collectively, our data suggests that the modulation of CD44/xCT, by reducing GSH levels and favoring the anaerobic metabolic switch might be an effective strategy for inducing CSC death.
E-mail address: [email protected] Acknowledgements Grants from Genoa University
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.217
P-71
Treatment with a low concentration of ionomycin induced neurite degeneration via influx of calcium ions, mitochondrial-dependent superoxide production and mitochondrial membrane oxidations. These phenomena were recorded by a time-lapse live imaging system. Finally, these neurite degeneration prevented by antioxidant vita.
E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.218
P-72
The effect of tocotrienols on high-fat diet-treated mice Yugo Kato 1, Masashi Shirai 1, Yoshinori Aoki 2, Taisuke Koike 2, Koji Fukui 1 1
Molecular Cell Biology Laboratory, Department of Bioscience and Engineering, Shibaura Institute of Technology, Tokyo, Japan 2 Mitsubishi-chemical foods corporation, Japan
Obesity is increasing in developed countries and is well known to a risk factor of severe diseases such as diabetes and Alzheimer's disease. Several kinds of evidence have been demonstrated that these diseases relate to oxidative damage. However, the detailed mechanisms of it relation have not yet elucidated. Previously, we reported that cognitive dysfunction is induced in normal aged- and vitamin E (V.E)-deficient mice models via accumulation of brain oxidation. On the basis of these data, we hypothesized that obesity increased the risk of cognitive dysfunction via brain oxidation. Tocotrienols (T3s) which are one kind of vitamin E have many biological functions. The most famous function of T3s is antioxidant, and the function is stronger than that of tocopherols. Other beneficial function of T3s is neuroprotection and inhibitory effect of HMG-CoA reductase. In this study, we assessed motor and cognitive function of long- and short-term high-fat diettreated mice in the presence or absence of T3s. Furthermore, we measured V. E, TBARS and antioxidant enzyme activity in these mice liver, serum and brain. These results indicate that obesity induce cognitive dysfunction via brain oxidation and treatment with T3s may show anti-obesity and neuroprotective effect in our model.
E-mail address: [email protected]
Influx of calcium ions accelerates neurite degeneration via induction of microtubule destabilization
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.219
Koji Fukui, Saki Nakamura, Shunsuke Okihiro Molecular Cell Biology Laboratory, Department of Bioscience and Engineering, Shibaura Institute of Technology, Tokyo, Japan
Reactive oxygen species (ROS) attack several living organs and induce neuronal cell death. Previously, we found that treatment with a low concentration of hydrogen peroxide induced neurite degeneration prior to the cell death. The neurites showed abnormal morphologies including beads formation, shrinkage and fragmentation. This phenomenon also observed in hippocampus of the normal-aged and vitamin E-deficient mice. In order to clarify the mechanism of neurite degeneration, we measured lipid peroxidative products in hydrogen peroxide-treated cells. The LOOH levels were significantly increased compared to the untreated group. If cell membranes are oxidized by ROS, large parts of receptors and ion channels may be also damaged. Here, we show the elucidation of the relationship between calcium influx and neurite degeneration in cultured neurons. Treatment with an ionomycin (calcium ionophore) induced neuronal cell death in a concentration- and a time-dependent manner.
P-73
Neutrophils activation by carbon nanotubes functionalized with COOH-groups and conjugated with DNA Tatsiana Kulahava 1, Lena Golubewa 1, Nikita Vasilieu 1, Olesya Paddubskaya 2, Mikhail Shuba 2 1 Department of Biophysics, Physics Faculty, Belarusian State University, Minsk, Belarus 2 Research Institute for Nuclear Problems, Belarusian State University, Minsk, Belarus
Interaction of neutrophils with carbon nanotubes (CNT), 100–400 nm in length, functionalized with -COOH groups and non-covalently