• Title/Summary/Keyword: oxidative DNA damage

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Mitochondrial Efficiency-Dependent Viability of Saccharomyces cerevisiae Mutants Carrying Individual Electron Transport Chain Component Deletions

  • Kwon, Young-Yon;Choi, Kyung-Mi;Cho, ChangYeon;Lee, Cheol-Koo
    • Molecules and Cells
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    • v.38 no.12
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    • pp.1054-1063
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    • 2015
  • Mitochondria play a crucial role in eukaryotic cells; the mitochondrial electron transport chain (ETC) generates adenosine triphosphate (ATP), which serves as an energy source for numerous critical cellular activities. However, the ETC also generates deleterious reactive oxygen species (ROS) as a natural byproduct of oxidative phosphorylation. ROS are considered the major cause of aging because they damage proteins, lipids, and DNA by oxidation. We analyzed the chronological life span, growth phenotype, mitochondrial membrane potential (MMP), and intracellular ATP and mitochondrial superoxide levels of 33 single ETC component-deleted strains during the chronological aging process. Among the ETC mutant strains, 14 ($sdh1{\Delta}$, $sdh2{\Delta}$, $sdh4{\Delta}$, $cor1{\Delta}$, $cyt1{\Delta}$, $qcr7{\Delta}$, $qcr8{\Delta}$, $rip1{\Delta}$, $cox6{\Delta}$, $cox7{\Delta}$, $cox9{\Delta}$, $atp4{\Delta}$, $atp7{\Delta}$, and $atp17{\Delta}$) showed a significantly shorter life span. The deleted genes encode important elements of the ETC components succinate dehydrogenase (complex II) and cytochrome c oxidase (complex IV), and some of the deletions lead to structural instability of the membrane-$F_1F_0$-ATP synthase due to mutations in the stator stalk (complex V). These short-lived strains generated higher superoxide levels and produced lower ATP levels without alteration of MMP. In summary, ETC mutations decreased the life span of yeast due to impaired mitochondrial efficiency.

Transcriptomic Analysis of Rat Brain Tissue Following Gamma Knife Surgery: Early and Distinct Bilateral Effects in the Un-Irradiated Striatum

  • Hirano, Misato;Shibato, Junko;Rakwal, Randeep;Kouyama, Nobuo;Katayama, Yoko;Hayashi, Motohiro;Masuo, Yoshinori
    • Molecules and Cells
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    • v.27 no.2
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    • pp.263-268
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    • 2009
  • Gamma knife surgery (GKS) is used for the treatment of various human brain disorders. However, the biological effects of gamma ray irradiation on both the target area, and the surrounding tissues are not well studied. The effects of gamma ray exposure to both targeted and untargeted regions were therefore evaluated by monitoring gene expression changes in the unilateral irradiated (60 Gy) and contralateral un-irradiated striata in the rat. Striata of irradiated and control brains were dissected 16 hours post-irradiation for analysis using a whole genome 44K DNA oligo microarray approach. The results revealed 230 induced and 144 repressed genes in the irradiated striatum and 432 induced and 239 repressed genes in the unirradiated striatum. Out of these altered genes 39 of the induced and 16 of the reduced genes were common to both irradiated and un-irradiated tissue. Results of semiquantitative, confirmatory RT-PCR and western blot analyses suggested that ${\gamma}$-irradiation caused cellular damage, including oxidative stress, in the striata of both hemispheres of the brains of treated animals.

A Study on the Radioprotective Effects of Foods -Focusing on the Glycobiological Properties of Mushrooms- (식품류를 이용한 방사선 방호 효과 -버섯류의 당 생물학적인 특징중심으로-)

  • Kim, Jong-Soo;Ahn, Byeong-Kwon;Choi, Hyun-Suk;Choi, Du-Bok;Yeom, Jung-Min;Kim, Soong-Pyung;Lee, In-Sung;Cho, Mi-Ja;Cha, Wol-Suk
    • KSBB Journal
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    • v.30 no.1
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    • pp.11-20
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    • 2015
  • Radiation causes various pathophysiological alterations in living animals, and it causes death at high doses by multiple mechanisms, including direct DNA damage and indirect oxidative stress. The search for useful radioprotectors has been an important issue in the field of radiation biology. Ideal radioprotectors should have low toxicity and an extended window of protection. As many synthetic compounds have toxic side effects, the natural products have attracted scientific attention as radioprotectors. Natural products that have been recently shown to be effective with various biological activities were found to have radioprotective effect. The aim of this review is to summary the recent research of the radioprotective effects of natural foods, especially focused on the glycobiological properties of mushrooms.

The Scavenging Effect on Nitric Oxide in Carthami Flos Herbal-Acupunture Solution (홍화 약침액의 Nitric Oxide에 대한 소거효과)

  • Woo, Dong-Su;Lee, Kyung-Min;Lee, Bong-Hyo;Lim, Seong-Chul;Jung, Tae-Young;Seo, Jung-Chul
    • Journal of Pharmacopuncture
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    • v.10 no.2 s.23
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    • pp.25-30
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    • 2007
  • Objectives : Free radical metabolism seems to occupy a remarkably common position in the mechanisms of aging and aging related disease. Oxidative damage to DNA, lipids. proteins and other molecules may contribute to the development of cancer, cardiovascular disease and possibly neurodegenerative disease. This study was designed to find out whether Carthami Flos Herbal-Acupuncture Solution can scavenge Nitric Oxide(NO) or not. SNAP is NO generator. NO concentration was estimated after 2,6, 12 and 24 hrs in no treatment group, after treatment with Vit. C or 1, 10, 100${\mu}$g/m1 of Carthami Flos Herbal-Acupuncture Solution. There was no significant scavenging effect of Carthami Flos Herbal-Acupuncture Solutionon NO after 2 hrs. But there was a significant scavenging effect of Cafhami Flos Herbal-Acupuncture Solution on NO in 10${\mu}$/m1 group after 6hrs. And there was a significant scavenging effect of carthami Flos Herbal-Acupuncture Solution on NO in 1, 10${\mu}$g/ml group after 12, 24 hrs. These results suggest that Carhami Flos Herbal-Acupuncture Solution has scavenging effect on NO. This study shows that Carthami Flos Herbal-Acupuncture Solution can be used for aging related disease and further studies are required to investigate the antioxidative effects of it.

Protective Effect of Hwansodan in Serum and Glucose Deprivation Induced-apoptotic Death of PC12 Cells Via Ho-1 Expression (영양혈청 결핍성 PC12 세포고사에서 HO-1의 발현 증가를 통한 환소단의 보호 효과)

  • Jung, Jae-Eun;Kim, Jin-Kyung;Kang, Baek-Gyu;Park, Chan-Ny;Park, Rae-Kil;Moon, Byung-Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1459-1466
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    • 2006
  • The water extract of Hwansodan has been traditionally used for treatment of ischemic brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of Hwansodan rescues cells from neurodegenerative disease. PC12 pheochromocytoma cells have been used extensively as a model for studying the cellular and molecular mechanisms of neuronal cell damages. Under deprivation of growth factor and ischemic injury, PC12 cells spontaneously undergoes apoptotic cell death. Serum and glucose deprivation markedly decreased the viability of PC12 cells, which was characterized with apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the aqueous extract of Hwansodan significantly reduced serum and glucose deprivation-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Pretreatment of Hwansodan also ingibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 was completely abolished in serum and glucose deprivated cells. Furthermore, pretreatment of Hwansodan obviously increased heme oxygenase 1 (HO-1) expression in PC12 cells. Taken together, the data suggest that the protective effects of Hwansodan against serum and glucose deprivation induced oxidative injuries may be achieved through the scavenging of reactive oxygene species accompanying with HO-1 induction.

Suboptimal Mitochondrial Activity Facilitates Nuclear Heat Shock Responses for Proteostasis and Genome Stability

  • Dongkeun Park;Youngim Yu;Ji-hyung Kim;Jongbin Lee;Jongmin Park;Kido Hong;Jeong-Kon Seo;Chunghun Lim;Kyung-Tai Min
    • Molecules and Cells
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    • v.46 no.6
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    • pp.374-386
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    • 2023
  • Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.

Protective Effect of Kefir Grain Against Dextran Sodium Sulfate-Induced Colitis in Rats (Dextran Sodium Sulfate로 대장염을 유도한 흰쥐에서 캐피어 원말의 장보호 효과)

  • Ko, Young-Eun;Kim, Mi-Kyoung;Cho, Han-Young;Lee, In-Young;Ly, Sun-Yung
    • Journal of Nutrition and Health
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    • v.41 no.5
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    • pp.391-401
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    • 2008
  • Probiotics have emerged as a potential treatment modality for numerous gastrointestinal disorders, including IBD. However, few probiotics have undergone appropriate preclinical screening in vivo. Kefir is considered a probiotic, benefiting the host through its effects in the intestinal tract. Despite numerous studies examining the action of probiotics on the host organism, few have analyzed the effects on intestinal environment. We assessed the protective effect of kefir for three weeks before inducing colitis with 2% dextran sodium sulfate for five days. The DSS loads were similar in all DSS treatment group. The results of the experiment are as follows. Food intake and FER of experimental groups were not significantly different each other, but water consumption tended to be higher in all DSS treatment groups as compared with the normal control. And visual inspection of feces revealed mild diarrhea in rat given 2% DSS. The anti-inflammatory activity of kefir was determined by myeloperoxidase activity during the DSS treatment, and there was no significant difference in any group. The levels of thiobarbituric acid reactive substances (TBARS) as a colonic lipid peroxidation were significantly lower in the kefir intake groups than in rats treated with 2% DSS alone. The DNA % in tail and tail moment values as a DNA damage level of the blood lymphocytes in kefir intake groups tended to be lower than 2% DSS treatment alone, especially tail lengths were significantly diminished. According to the colonic histopathological assay, there were a severe inflammation of lamina propria and submucosa and mild edema in mucosa and sub mucosa in DSS alone treated group. We found a slight regenerative change in kefir treatment groups. In our experiments, this means that ulcerative colitis related to oxidative injury might be prevented by kefir as a probiotic. Further studies of the potential benefits of kefir as a probiotic in inflammatory condition are encouraged.

The Effect of Antioxidant Vitamins on Aflatoxin $B_{1}-DNA$ Adduct the Formation in Aflatoxin $B_1$ Administered Mice Liver (항산화비타민이 Aflatoxin $B_1$ 투여 마우스의 간세포에서 Aflatoxin $B_{1}-DNA$ Adduct 형성에 미치는 영향)

  • Park, Seon-Ja;Kang, Sung-Jo;Park, Jung-Hyun;Oh, Sang-Suk;Chung, Duck-Hwa
    • Korean Journal of Food Science and Technology
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    • v.33 no.6
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    • pp.669-675
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    • 2001
  • The objective of this study was to examine the effects of antioxidant vitamins on the formation of $AFB_{1}-DNA$ adduct and $AFB_{1}-inducing$ cellular oxidative damage. Intraperitoneal(i.p.)injections of 10 mg/kg vitamin C(VC) and 63.8 mg/kg vitamin E(VE) were repeatedly administrated 4 times with 2 days interval to 6 week old male ICR mice. After one hour of vitamin treatments, 0.4 mg/kg $AFB_1$ was injected in $AFB_1$ plus vitamin treated groups by same way. On the other hands, $AFB_1$ treated group was only injected with $AFB_1$ by the same method described above without vitamins. According to quantitative analysis of the $AFB_1$ in mice serum by indirect competitive ELISA, 12.28 and 18.78 ng/mL were detected in $AFB_1-treated$ groups, but 7.60 and 4.85 ng/mL in $AFB_1$ plus VC and VE treated groups, respectively. 23.78, 25.48 ng/mL of $AFB_1-DNA$ adduct were detected in mice liver of $AFB_1$treated groups, while 5.26, 7.81 ng/mL in $AFB_1$ plus VC and VE treated groups, respectively. Consequently, the differences in the concentrations of $AFB_1$ related materials between vitamin treated and non-treated groups were significant. Immunohistochemistry revealed brownish infiltration of $AFB_1$ around central vein and sinusoid in $AFB_1-treated$ group. This manifestation was distinctly reduced in $AFB_1$ plus VC and VE treated groups.

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Overexpression of Ice Recrystallization Inhibition Protein (HvIRIP) from Barley Enhances Cold Tolerance in Transgenic rapeseed plants (HvIRIP 과발현 유채 형질전환체의 내한성 증진)

  • Roh, Kyung Hee;Park, Jong-Sug;Kang, Han-Chul;Kim, Jong-Bum;Jang, Young-Suk;Kim, Kwang-Soo;Yi, Hankuil
    • Journal of Applied Biological Chemistry
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    • v.58 no.4
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    • pp.325-332
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    • 2015
  • Rapeseed (Brassica napus) is now the second largest oilseed crop after soybean. Cold temperature tolerance is an important agronomic trait in winter rapeseed that determines the plant's ability to control below freezing temperatures. To improve cold tolerance of rapeseed plants, an expression vector containing an Barley Ice recrystallization inhibition protein (HvIRIP) cDNA driven by a cauliflower mosaic virus 35S promoter was transferred into rapeseed plants. Transgenic expression of HvIRIP was proved by southern- and northern-blot analyses. The level of freezing tolerance of transgenic $T_3$ plants was found to be significantly greater than that of wild-type rapeseed plants by freezing assay. Proline accumulation during cold stress was also highly induced in the transgenic rapeseed plants. The transgenic plants exhibited considerable tolerance against oxidative damage induced by cold stress. Our results indicated that heterologous HvIRIP expression in transgenic rapeseed plants may induce several oxidative-stress responsive genes to protect from cold stress.

Identification and Molecular Characterization of Methionine Sulfoxide Reductase B Gene in Rice Blast Fungus, Magnaporthe oryzae (벼도열병균에서의 methionine sulfoxide reductase B 유전자의 분자적 특성)

  • Kim, Jeong-Hwan;Kim, Jin-Soo;Jeong, Mi-Yeon;Choi, Woo-Bong
    • Journal of Life Science
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    • v.19 no.3
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    • pp.343-348
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    • 2009
  • Magnaporthe oryzae, a major cause of rice blast, is one of the most destructive plant fungal pathogens. Secretion of reactive oxygen species (ROS) during the infection phase of plant pathogenic fungus plays a key role in the defense mechanism of a plant. ROS causes oxidative damage and functional modification to the proteins in a pathogenic fungus. Methionine, especially, is a major target of ROS, which oxidizes it to methionine sulfoxide. To survive from the attack of ROS, plant pathogenic fungus has antioxidative systems - one example would be methionine sulfoxide reductase B (MSRB), which reverses the oxidative alteration of methionine to methionine sulfoxide. In the present study, identification and molecular characterization of the MSRB gene in M. oryzae KJ201 were investigated. The MSRB gene was amplified by PCR from the M. oryzae KJ201 genomic DNA. The copy number of MSRB in the genome of M. oryzae KJ201 was identified by Southern blot analysis, which revealed that the gene exists as a single copy. To study the molecular function of an MSRB gene, the expression level of the MSRB gene was assayed with hydrogen peroxide treatment by Northern blot analysis and RT-PCR. The expression of the MSRB gene was increased by treatment of hydrogen peroxide, without significant correlation to hydrogen peroxide concentrations. These results indicate that the MSRB gene in M. oryzae KJ201 could contribute to protection against plant defense compounds such as ROS and offer a novel strategy for the control of rice blast.