BMB Reports : Poly(ADP-ribose) protects vascular smooth muscle cells from oxidative DNA damage

( Chao Zhang ),( Tao Luo ),( Shijun Cui ),( Yongquan Gu ),( Chunjing Bian ),( Yibin Chen ),( Xiaochun Yu ),( Zhonggao Wang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.6

Vascular smooth muscle cells (VSMCs) undergo death during atherosclerosis, a widespread cardiovascular disease. Recent studies suggest that oxidative damage occurs in VSMCs and induces atherosclerosis. Here, we analyzed oxidative damage repair in VSMCs and found that VSMCs are hypersensitive to oxidative damage. Further analysis showed that oxidative damage repair in VSMCs is suppressed by a low level of poly (ADP-ribosyl)ation (PARylation), a key post-translational modification in oxidative damage repair. The low level of PARylation is not caused by the lack of PARP-1, the major poly(ADP-ribose) polymerase activated by oxidative damage. Instead, the expression of poly(ADP-ribose) glycohydrolase, PARG, the enzyme hydrolyzing poly(ADP-ribose), is significantly higher in VSMCs than that in the control cells. Using PARG inhibitor to suppress PARG activity facilitates oxidative damage-induced PARylation as well as DNA damage repair. Thus, our study demonstrates a novel molecular mechanism for oxidative damage-induced VSMCs death. This study also identifies the use of PARG inhibitors as a potential treatment for atherosclerosis. [BMB Reports 2015; 48(6): 354-359]

Glutathione S-transferase (GST) 유전자 다형성에 따른 우리나라 젊은 성인의 항산화 상태, DNA 손상 및 지질 양상

조혜련 (Jo,Hye-Ryun ),이혜진 (Lee,Hye-Jin ),강명희 (Kang,Myung-Hee ) 韓國營養學會 2011 Journal of Nutrition and Health Vol.44 No.1

Oxidative stress leads to the induction of cellular oxidative damage, which may cause adverse modifications of DNA, proteins, and lipids. The production of reactive species during oxidative stress contributes to the pathogenesis of many diseases. Antioxidant defenses can neutralize reactive oxygen species and protect against oxidative damage. The aim of this study was to assess the antioxidant status and the degree of DNA damage in Korean young adults using glutathione s-transferase (GST) polymorphisms. The GSTM1 and GSTT1 genotypes were characterized in 245 healthy young adults by smoking status, and their oxidative DNA damage in lymphocytes and antioxidant status were assessed by GST genotype. General characteristics were investigated by simple questionnaire. From the blood of the subjects, GST genotypes; degree of DNA damage in lymphocytes; the erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase; plasma concentrations of total peroxyl radical-trapping potential (TRAP), vitamin C, α- and γ-tocopherol, α- and β-carotene and cryptoxanthin, as well as plasma lipid profiles, conjugated diene (CD), GOT, and GPT were analyzed. Of the 245 subjects studied, 23.2% were GSTM1 wild genotypes and 33.4% were GSTT1 wild genotype. No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and the plasma TRAP level, CD, GOT, and GPT levels were observed between smokers and non-smokers categorized by GSTM1 or GSTT1 genotype. Plasma levels of α- and γ-tocopherol increased significantly in smokers with the GSTT1 wild genotype (p < 0.05); however, plasma level of α-carotene decreased significantly in non-smokers with the GSTM1 wild genotype (p < 0.05). DNA damage assessed by the Comet assay was significantly higher in non-smokers with the GSTM1 null genotype; whereas DNA damage was significantly lower in non-smokers with the GSTT1 null genotype. Total cholesterol and LDL cholesterol levels were significantly higher in non-smokers with the GSTT1 null genotype than those with the GSTT1 wild genotype (p < 0.05). In conclusion, the GSTM1 null genotype or the GSTT1 wild genotype in non-smokers aggravated their antioxidant status through DNA damage of lymphocytes; however, the GSTT1 wild type in non-smokers had normal plasma total cholesterol and LDL-cholesterol levels. This finding confirms that GST polymorphisms could be an important determinant of antioxidant status and plasma lipid profiles in non-smoking young adults. Further study is necessary to clarify the antioxidant status and/or lipid profiles of smokers with the GST polymorphism and to conduct a study with significantly more subjects. (Korean J Nutr 2011 44(1): 16 ~ 28)

Reduction of TNFα-induced Oxidative DNA Damage Product, 8-Hydroxy-2′-Deoxyguanosine, in L929 Cells Stably Transfected with Small Heat Shock Protein

Young-Mee Park,Eun-Mi Choi 대한생리학회-대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.2

<P> Previous studies have demonstrated that oxidative stress involving generation of reactive oxygen species (ROS) is responsible for the cytotoxic action of TNFα. Protective effect of small heat shock proteins (small HSP) against diverse oxidative stress conditions has been suggeted. Although overexpression of small hsp was shown to provide an enhanced survival of TNFα-sensitive cells when challenged with TNFα, neither the nature of TNFα-induced cytotoxicity nor the protective mechanism of small HSP has not been completely understood. In this study, we have attempted to determine whether TNFα induces oxidative DNA damage in TNFα-sensitive L929 cells. We chose to measure the level of 8-hydroxy-2′-deoxyguanosine (8 ohdG), which has been increasingly recognized as one of the most sensitive markers of oxidative DNA damage. Our results clearly demonstrated that the level of 8 ohdG increased in L929 cells in a TNFα dose-dependent manner. Subsequently, we asked whether small HSP has a protective effect on TNFα-induced oxidative DNA damage. To accomplish this goal, we have stably transfected L929 cells with mouse small hsp cDNA (hsp25) since these cells are devoid of endogenous small hsps. We found that TNFα-induced 8 ohdG was decreased in cells overexpressing exogenous small hsp. We also found that the cell killing activity of TNFα was decreased in these cells as measured by clonogenic survival. Taken together, results from the current study show that cytotoxic mechanism of TNFα involves oxidative damage of DNA and that overexpression of the small hsp reduces this oxidative damage. We suggest that the reduction of oxidative DNA damage is one of the most important protective mechanisms of small HSP against TNFα.

Buddleja officinalis prevents the normal cells from oxidative damage via antioxidant activity

Hong, Se-Chul,Jeong, Jin-Boo,Jeong, Hyung-Jin The Plant Resources Society of Korea 2008 한국자원식물학회지 Vol.21 No.6

The flowers of Buddleja officinalis are used to treat sore and damaged eyes, a condition which is similar to skin wounds. However, whether it has any protective effect on oxidative DNA damage and cell death induced by hydroxyl radical remains unclear. In this study, we evaluated the protective effects of the extracts against oxidative DNA and cell damage caused by hydroxyl radical. DPPH radical, hydroxyl radical, hydrogen peroxide and intracellular ROS scavenging assay, and $Fe^{2+}$ chelating assay were used to evaluate the antioxidant properties. phi X 174 RF I plasmid DNA and intracellular DNA migration assay were used to evaluate the protective effect against oxidative DNA damage. Lastly, MTT assay and lipid peroxidation assay were used to evaluate the protective effect against oxidative cell damage. It was found to prevent intracellular DNA and the normal cells from oxidative damage caused by hydroxyl radical via antioxidant activities. These results suggest that Buddleja officinalis may exert the inhibitory effect on ROS-induced carcinogenesis by blocking oxidative DNA damage and cell death.

Reduction of TNE ${\alpha}-induced$ Oxidative DNA Damage Product, 8-Hydroxy-2'-Deoxyguanosine, in L929 Cells Stably Transfected with Small Heat Shock Protein

Park, Young-Mee,Choi, Eun-Mi The Korean Society of Pharmacology 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.2

Previous studies have demonstrated that oxidative stress involving generation of reactive oxygen species (ROS) is responsible for the cytotoxic action of $TNF{\alpha}$. Protective effect of small heat shock proteins (small HSP) against diverse oxidative stress conditions has been suggeted. Although overexpression of small hsp was shown to provide an enhanced survival of $TNF{\alpha}$-sensitive cells when challenged with $TNF{\alpha}$, neither the nature of $TNF{\alpha}$-induced cytotoxicity nor the protective mechanism of small HSP has not been completely understood. In this study, we have attempted to determine whether $TNF{\alpha}$ induces oxidative DNA damage in $TNF{\alpha}$-sensitive L929 cells. We chose to measure the level of 8-hydroxy-2'-deoxyguanosine (8 ohdG), which has been increasingly recognized as one of the most sensitive markers of oxidative DNA damage. Our results clearly demonstrated that the level of 8 ohdG increased in L929 cells in a $TNF{\alpha}$ dose-dependent manner. Subsequently, we asked whether small HSP has a protective effect on $TNF{\alpha}$-induced oxidative DNA damage. To accomplish this goal, we have stably transfected L929 cells with mouse small hsp cDNA (hsp25) since these cells are devoid of endogenous small hsps. We found that $TNF{\alpha}$-induced 8 ohdG was decreased in cells overexpressing exogenous small hsp. We also found that the cell killing activity of $TNF{\alpha}$ was decreased in these cells as measured by clonogenic survival. Taken together, results from the current study show that cytotoxic mechanism of $TNF{\alpha}$ involves oxidative damage of DNA and that overexpression of the small hsp reduces this oxidative damage. We suggest that the reduction of oxidative DNA damage is one of the most important protective mechanisms of small HSP against $TNF{\alpha}$.

Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-κB Pathways

( Sung Hwan Kim ),( In Chul Lee ),( Je Won Ko ),( Chang Jong Moon ),( Sung Ho Kim ),( In Sik Shin ),( Young Won Seo ),( Hyoung Chin Kim ),( Jong Choon Kim ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.2

This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-κB, COX-2, iNOS, TNF-α, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-κB, COX-2, iNOS, TNF-α, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF- κB and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.

흡연 여부에 따른 Glutathione S-transferase (GST) M1 및 T1 유전자 다형성이 우리나라 젊은 성인의 임파구 DNA 손상과 항산화 영양상태 지표들 간의 관련성에 미치는 영향

한정화(Han Jeong-Hwa),이혜진(Lee Hye-Jin),강명희(Kang Myung-Hee) 한국영양학회 2011 Journal of Nutrition and Health Vol.44 No.5

Glutathione S-transferase (GST) is a multigene family of phase II detoxifying enzymes that metabolize a wide range of exogenous and endogenous electrophilic compounds. GSTM1 and GSTT1 gene polymorphisms may account for inter-individual variability in coping with oxidative stress. We investigated the relationships between the level of lymphocyte DNA and antioxidative parameters and the effect on GST genotypes. GSTM1 and GSTT1 were characterized in 301 young healthy Korean adults and compared with oxidative stress parameters such as the level of lymphocyte DNA plasma antioxidant vitamins and erythrocyte antioxidant enzymes in smokers and non smokers. GST genotype degree of DNA damage in lymphocytes erythrocyte activities of superoxide dismutase catalase and glutathione peroxidase (GSH-Px) and plasma concentrations of total radical-trapping antioxidant potential (TRAP) vitamin C α- and γ-tocopherol α- and β-carotene and cryptoxanthin were analyzed. Lymphocyte DNA damage assessed by the comet assay was higher in smokers than that in non-smokers but the levels of plasma vitamin C β-carotene TRAP erythrocyte catalase and GSH-Px were lower than those of non-smokers (p < 0.05). Lymphocyte DNA damage was higher in subjects with the GSTM1-null or GSTT1-present genotype than those with the GSTM1-present or GSTT1-null genotype. No difference in erythrocyte antioxidant enzyme activities plasma TRAP or vitamin levels was observed in subjects with the GSTM1 or GSTT1 genotypes except β-carotene. Significant negative correlations were observed between lymphocyte DNA damage and plasma levels of TRAP and erythrocyte activities of catalase and GSH-Px after adjusting for smoking pack-years. Negative correlations were observed between plasma vitamin C and lymphocyte DNA damage only in individuals with the GSTM1-present or GSTT1-null genotype. The interesting finding was the significant positive correlations between lymphocyte DNA damage and plasma levels of α-carotene β-carotene and cryptoxanthin. In conclusion the GSTM1-null and GSTT1-present genotypes as well as smoking aggravated antioxidant status through lymphocyte DNA damage. This finding confirms that GST polymorphisms could be important determinants of antioxidant status in young smoking and non-smoking adults. Consequently the protective effect of supplemental antioxidants on DNA damage in individuals carrying the GSTM1-null or GSTT1-present genotypes might show significantly higher values than expected.

The root extract of Paeonia lactiflora Pall inhibits the oxidative damage via its anti-oxidant activity

Ji Young Yun,Jin Boo Jeong,Hyun Ji Eo,Kun Woo Kwon,Se Chul Hong,Hyung Jin Jeong,Jin Suk Koo 대한본초학회 2012 大韓本草學會誌 Vol.27 No.6

Objectives: Reactive oxygen species (ROS) have been associated with pathogenic processes including carcinogenesis through direct effect on DNA directly and by acting as a tumor promoter. Therefore, it has been regarded that ROS may be a major target for cancer prevention. The root of Paeonia lactiflora pall (PL), a traditional Chinese herb, has been a component of effective prescriptions for treatment of liver disease. Also, there are some reports about the antioxidant activities of the extracts from PL. However, little has been known about the effects of PL against oxidative damage. This work aimed to elucidate the anti-oxidant effects of Paeonia lactiflora pall (PL) in the non-cellular system and cellular system. Methods: Antioxidant activities of PL were evaluated by hydroxyl radical scavenging assay and Fe2+ chelating assay. Anti-oxidative effect of PL was evaluated by φX-174 RF I plasmid DNA cleavage assay in non-cellular system. In addition, DNA migration assay, expression level of phospho-H2AX, MTT assay and lipid peroxidation assay were performed for evaluate the anti-oxidative effect of PL in cellular system. Results: PL had a dose-dependent hydroxyl radical scavenging and Fe2+ chelating capacity. In addition, PL inhibited oxidative DNA and cell damage induced by hydroxyl radical in non-cellular system and cellular system. Conclusion: Taken together, P. lactiflora pall may be possible for the application to a potential drug for treating the oxidative diseases such as cancer.

The root extract of Paeonia lactiflora Pall inhibits the oxidative damage via its anti-oxidant activity

Yun, Ji Young,Jeong, Jin Boo,Eo, Hyun Ji,Kwon, Kun Woo,Hong, Se Chul,Jeong, Hyung Jin,Koo, Jin Suk The Korea Association of Herbology 2012 大韓本草學會誌 Vol.27 No.6

Objectives : Reactive oxygen species (ROS) have been associated with pathogenic processes including carcinogenesis through direct effect on DNA directly and by acting as a tumor promoter. Therefore, it has been regarded that ROS may be a major target for cancer prevention. The root of Paeonia lactiflora pall (PL), a traditional Chinese herb, has been a component of effective prescriptions for treatment of liver disease. Also, there are some reports about the antioxidant activities of the extracts from PL. However, little has been known about the effects of PL against oxidative damage. This work aimed to elucidate the anti-oxidant effects of Paeonia lactiflora pall (PL) in the non-cellular system and cellular system. Methods : Antioxidant activities of PL were evaluated by hydroxyl radical scavenging assay and $Fe^{2+}$ chelating assay. Anti-oxidative effect of PL was evaluated by ${\varphi}X$-174 RF I plasmid DNA cleavage assay in non-cellular system. In addition, DNA migration assay, expression level of phospho-H2AX, MTT assay and lipid peroxidation assay were performed for evaluate the anti-oxidative effect of PL in cellular system. Results : PL had a dose-dependent hydroxyl radical scavenging and $Fe^{2+}$ chelating capacity. In addition, PL inhibited oxidative DNA and cell damage induced by hydroxyl radical in non-cellular system and cellular system. Conclusion : Taken together, P. lactiflora pall may be possible for the application to a potential drug for treating the oxidative diseases such as cancer.

Wig Damage Related Repair and PROTECTION Clinic Utilizing Oxidation Potential Solution

Youngjoo Lee J-INSTITUTE 2021 Protection Convergence Vol.6 No.4

Purpose: The purpose of this study is to examine and understand the effects of oxidation potential solution treatment which does not cause an environmental pollution and hair damages when hair is damaged by repeated washing, perming, and dyeing of wigs, etc., and this study is meaningful in that it provides the basic data which may properly be use for an environmentally friendly oxidation potential solution in the field of beauty. Method: Soak the damaged and tangled wigs in a reduction potential solution of pH 11 for 30 minutes to remove wastes and shampoo, then apply the treatment and let it sit naturally for 30 minutes, then classified the control group which rinsed clinic with tap water without undergoing the oxidative potential water treatment and the experimental group which rinsed clinic with the oxidation potential solution, thereby comparatively analyzing the extent of entanglement, elasticity, and gloss of the hair. Results: First, the hair was immersed in a reduction potential solution of pH 11 for 30 minutes, then shampooed. Consequently, it was discovered that both the experimental group and the control group did not get their hair entangled any more. Second, the control group at which the treatment was rinsed with tap water had even more entangled hair and even after they were combed, they looked stretched and poor. In the experimental group which rinsed with the oxidation potential solution, the tangled hair became loose, combing was made easier, and the hair s gloss and softness turned out relatively well. Conclusion: Based on the information above, it was demonstrated that the extent of damages for the control group’s wigs without the oxidation potential solution treatment increased during shampooing, while the experimental group’s wigs treated with the oxidation potential solution demonstrated little damages and maintained elastic hair. This is because the product is completed by removing the cuticles from the hair with acid treatment during the wig’s manufacturing process to prevent the entanglement of the hair, and hence, with an alkaline shampoo, almost no cuticles are left behind, making them rough, and the loss of polypeptide in the hair increases the damages. Meanwhile, the oxidation potential solution(pH 2-11) has a lower chlorine concentration compared to the general chlorine based disinfectants, and hence, it is easy to decompose and does not cause environmental pollution, and it was also confirmed that there is no further damage caused to the hair as there is no secondary damage given the residues because it is reduced to its properties.