- Email: [email protected]
High cholesterol diet-mediated unfolded protein response activation enhances autophagic cell death in heart tissue
S56
D. Rossin et al. / Free Radical Biology and Medicine 108 (2017) S18–S107
The effect of progesterone, estradiol (100 nM) and insulin (10 nM) was investigated in vitro using HL60 and ex vivo with stimulated peripheral blood mononuclearPBMC and PBMC's. The study included 4 main groups (non-pregnant with/without hormonal contraceptives, diabetic, pregnant, and GD women). The genomic damage was examined using comet assay and micronucleus frequency test. The female hormones mediated DNA damage in HL60 and stimulated PBMC's. Hormonal contraceptive users showed no significant DNA damage compared with non-pregnant women control. The DNA damage was significantly induced in pregnant compared with non-pregnant women. The DNA damage seems to be significantly induced in GD women, while reduction in DNA damage is observed after delivery. The higher DNA damage in pregnant women could be due to the changes of female hormones and in gestational diabetes due to high insulin levels in the blood. Altogether, mechanistic reasons of the alterations concerning cancer risk need to be investigated. E-mail address: [email protected] (E. Awad) http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.197
P-113
Antioxidant activity of Crataegus Monogyna L flowers Sibel Konyalioglu 3, Gozde Elgin Cebe 1, Selin Aktar 2 1
Ege University, Pharmacy Faculty, Department of Biochemistry, Izmir, Turkey 2 Ege University, Pharmacy Faculty, Department of Pharmaceutical Botany, Izmir, Turkey 3 Ege University, Pharmacy Faculty, Department of Pharmaceutical Botany Izmir, Turkey Keywords: Flowers of Crataegus Monogyna; TEAC; CUPRAC; Rutin
Crataegus species are known by their biological effects for many years. Crataegus monogyna Jacq. flowers have been ethnomedically used in different parts of Turkey for their many biological effects such as against tachycardia and sedative, antihypertensive, antispasmodic and diuretic. In addition to the widespread use of Crataegus species, many pharmacopoeias and monografts are registered, and a large number of in vitro, in vivo and clinical studies have been carried out with respect to bioactivity and mechanism of action. In vitro, leaves and fruits of Crataegusspecies have also been shown to exhibit antioxidant. However, these properties are influenced by the type of plant organ, the harvest season, the species and the geographical origin. In this contex, different extracts of ripe flowers of Crataegus monogyna (CM) collected from natural habitats on the limit of Konya/Seydişehir-Turkey at September 2015 were evaluated for their antioxidant capacity. Rutin contents was determined as 2.68 μg/ml in ethanolic extract of Crataegus monogyna Jacq., % ABTS radical scavenging activity of the extract is 78.80 7 4.09 and 1.080 7 0.08 μg trolox/mg extract in CUPRAC method. In conclusion, the results of this study indicate that flowers of Crataegus monogyna provide considerable antioxidant protection and can be suitable raw material for the medicine, food and cosmetic industries.
P-114
High cholesterol diet-mediated unfolded protein response activation enhances autophagic cell death in heart tissue Erdi Sozen 1, Burak Yazgan 1, Olgu Enis Tok 2, Feriha Ercan 2, Betul Karademir 1, Nesrin Kartal Ozer 1 1
Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research Center (GEMHAM), Marmara University 2 Department of Histology and Embriology, Faculty of Medicine, Marmara University,Turkey Keywords: Hypercholesterolemia; Autophagy; ER stress
The role of ER in the proper synthesis and correct folding of protein, to establish the homeostasis of organism, is well documented by various studies. Following excessive oxidative stress, the accumulation of unfolded/misfolded proteins increase in the lumen of ER which blocks the inhibitory effect of GRP78 on UPR regulatory proteins; IRE1, PERK and ATF6. It is clear that ER stress mediated UPR is a potent inducer of proteasomal and autophagic activities which serves as a degradation process for maintaining stress tolerance, limited damage and viability under stress conditions. Interestingly, aberrantly activation of autophagy can result in destroying major portions of the cytosol and organelles, which will lead to autophagic death of cardiac myocytes, and development of cardiac failure. In the present study Grp78, Grp94, pIRE1, pPERK, derlin-1, proteasome β5 subunit, VCP, beclin-1 and LC3-II, well known markers of ER stress, proteasomal and autophagic activities, are investigated in the heart tissue of rabbits. Furthermore, autophagic activity in heart tissue is observed in hypercholesterolemic vs control rabbits by electron microscopy. Additionally, colocalization studies of mitochondria and p62 in cryo sections of heart tissue were applied to understand the levels of mitochondria degradation by autophagy. E-mail address: [email protected] (E. Sozen) Acknowledgements
Supported by Marmara University Research Fund SAG-A130612-0202. http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.199
P-115
Cell cycle arest and regulation of Nrf 2 by Ganoderma lucidum in hepatocellular carcinoma Ali Mert Ozgonul 1, Sibel Konyalioglu 2, Guliz Armagan 3, Taner Dagci 4 1
Ege Ege 3 Ege 4 Ege 2
University, University, University, University,
Faculty Faculty Faculty Faculty
of of of of
Medicine, Izmir, Turkey Pharmacy, Izmir, Turkey Pharmacy, Izmir, Turkey Medicine, Izmir, Turkey
Keywords: Ganoderma lucidum; Nrf2; cell cycle arrest; hepatocellular carcinoma cell-line
E-mail address: [email protected] (S. Konyalioglu) http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.198
Currently, hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. However, the studies focusing on
D. Rossin et al. / Free Radical Biology and Medicine 108 (2017) S18–S107
The effect of progesterone, estradiol (100 nM) and insulin (10 nM) was investigated in vitro using HL60 and ex vivo with stimulated peripheral blood mononuclearPBMC and PBMC's. The study included 4 main groups (non-pregnant with/without hormonal contraceptives, diabetic, pregnant, and GD women). The genomic damage was examined using comet assay and micronucleus frequency test. The female hormones mediated DNA damage in HL60 and stimulated PBMC's. Hormonal contraceptive users showed no significant DNA damage compared with non-pregnant women control. The DNA damage was significantly induced in pregnant compared with non-pregnant women. The DNA damage seems to be significantly induced in GD women, while reduction in DNA damage is observed after delivery. The higher DNA damage in pregnant women could be due to the changes of female hormones and in gestational diabetes due to high insulin levels in the blood. Altogether, mechanistic reasons of the alterations concerning cancer risk need to be investigated. E-mail address: [email protected] (E. Awad) http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.197
P-113
Antioxidant activity of Crataegus Monogyna L flowers Sibel Konyalioglu 3, Gozde Elgin Cebe 1, Selin Aktar 2 1
Ege University, Pharmacy Faculty, Department of Biochemistry, Izmir, Turkey 2 Ege University, Pharmacy Faculty, Department of Pharmaceutical Botany, Izmir, Turkey 3 Ege University, Pharmacy Faculty, Department of Pharmaceutical Botany Izmir, Turkey Keywords: Flowers of Crataegus Monogyna; TEAC; CUPRAC; Rutin
Crataegus species are known by their biological effects for many years. Crataegus monogyna Jacq. flowers have been ethnomedically used in different parts of Turkey for their many biological effects such as against tachycardia and sedative, antihypertensive, antispasmodic and diuretic. In addition to the widespread use of Crataegus species, many pharmacopoeias and monografts are registered, and a large number of in vitro, in vivo and clinical studies have been carried out with respect to bioactivity and mechanism of action. In vitro, leaves and fruits of Crataegusspecies have also been shown to exhibit antioxidant. However, these properties are influenced by the type of plant organ, the harvest season, the species and the geographical origin. In this contex, different extracts of ripe flowers of Crataegus monogyna (CM) collected from natural habitats on the limit of Konya/Seydişehir-Turkey at September 2015 were evaluated for their antioxidant capacity. Rutin contents was determined as 2.68 μg/ml in ethanolic extract of Crataegus monogyna Jacq., % ABTS radical scavenging activity of the extract is 78.80 7 4.09 and 1.080 7 0.08 μg trolox/mg extract in CUPRAC method. In conclusion, the results of this study indicate that flowers of Crataegus monogyna provide considerable antioxidant protection and can be suitable raw material for the medicine, food and cosmetic industries.
P-114
High cholesterol diet-mediated unfolded protein response activation enhances autophagic cell death in heart tissue Erdi Sozen 1, Burak Yazgan 1, Olgu Enis Tok 2, Feriha Ercan 2, Betul Karademir 1, Nesrin Kartal Ozer 1 1
Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research Center (GEMHAM), Marmara University 2 Department of Histology and Embriology, Faculty of Medicine, Marmara University,Turkey Keywords: Hypercholesterolemia; Autophagy; ER stress
The role of ER in the proper synthesis and correct folding of protein, to establish the homeostasis of organism, is well documented by various studies. Following excessive oxidative stress, the accumulation of unfolded/misfolded proteins increase in the lumen of ER which blocks the inhibitory effect of GRP78 on UPR regulatory proteins; IRE1, PERK and ATF6. It is clear that ER stress mediated UPR is a potent inducer of proteasomal and autophagic activities which serves as a degradation process for maintaining stress tolerance, limited damage and viability under stress conditions. Interestingly, aberrantly activation of autophagy can result in destroying major portions of the cytosol and organelles, which will lead to autophagic death of cardiac myocytes, and development of cardiac failure. In the present study Grp78, Grp94, pIRE1, pPERK, derlin-1, proteasome β5 subunit, VCP, beclin-1 and LC3-II, well known markers of ER stress, proteasomal and autophagic activities, are investigated in the heart tissue of rabbits. Furthermore, autophagic activity in heart tissue is observed in hypercholesterolemic vs control rabbits by electron microscopy. Additionally, colocalization studies of mitochondria and p62 in cryo sections of heart tissue were applied to understand the levels of mitochondria degradation by autophagy. E-mail address: [email protected] (E. Sozen) Acknowledgements
Supported by Marmara University Research Fund SAG-A130612-0202. http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.199
P-115
Cell cycle arest and regulation of Nrf 2 by Ganoderma lucidum in hepatocellular carcinoma Ali Mert Ozgonul 1, Sibel Konyalioglu 2, Guliz Armagan 3, Taner Dagci 4 1
Ege Ege 3 Ege 4 Ege 2
University, University, University, University,
Faculty Faculty Faculty Faculty
of of of of
Medicine, Izmir, Turkey Pharmacy, Izmir, Turkey Pharmacy, Izmir, Turkey Medicine, Izmir, Turkey
Keywords: Ganoderma lucidum; Nrf2; cell cycle arrest; hepatocellular carcinoma cell-line
E-mail address: [email protected] (S. Konyalioglu) http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.198
Currently, hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. However, the studies focusing on