• Title/Summary/Keyword: Oxidative damage

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AMPK와 자식작용의 미토콘드리아 생합성 조절 기전 (Control Mechanism of AMPK and Autophagy for Mitochondrial Biogenesis)

  • 전병환
    • 한국콘텐츠학회논문지
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    • 제9권4호
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    • pp.355-363
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    • 2009
  • 비정상적인 미토콘드리아에 의해 산화 스트레스가 증가하면 세포내 신호전달 및 유전자 발현에 손상을 일으켜 인슐린 저항성이나 당뇨병 등의 여러 질환들을 유발한다. 그런데 자식작용은 산화 스트레스로 기능이 저하된 미토콘드리아를 제거하여 인슐린 저항성 등을 억제해준다. 한편 운동도 미토콘드리아 생합성을 강화시켜 조직의 기능저하나 퇴행을 회복시켜준다. 따라서 운동과 자식작용이 서로 연관되어 미토콘드리아 생합성을 유도하는 신호체계로 작용할 가능성이 있고, 이 연구를 통해 운동 혹은 AICAR (aminoimidazole-4-carboxamide-1-${\beta}$-D-ribofuranoside)처치로 활성 화된 AMPK(5'-AMP- activated protein kinase) 신호전달체계가 미토콘드리아 생합성을 증가시키는 경로에 자식작용이 관여하는지의 여부를 확인하고자 하였다. 연구결과에 따르면, 6시간의 급성운동으로 쥐의 골격근에서 PGC-1(peroxisome proliferator-activated receptor gamma coactivator 1)과 mtTFA (mitochondrial transcription factor A)의 mRNA 발현이 유의하게 증가하였다. 하지만 자식작용 표지제인 LC3(microtubule-associated proteinl light chain 3)의 mRNA 발현은 증가경향을 나타냈지만 유의하지 않았다. 한편 C2C12 근세포에서도 AICAR 처치에 의해 PGC-1, mtTFA mRNA 발현이 모두 증가하였지만, 이러한 증가는 LC3 SiRNA에 의해서 억제되지 않는 것으로 나타났다. 이러한 결과들을 통해 자식작용은 AMPK에 의해 조절되는 신호전달 전달체계와는 다른 경로로 미토콘드리아 생합성에 영향을 미칠 것으로 사료된다.

허혈 상태의 PC12 세포에 대한 대보원전(大補元煎)의 신경보호효과 (Neuroprotective Effects of Daebowonjeon on PC12 Cells Exposed to Ischemia)

  • 김봉상;이선우;문병순
    • 동의생리병리학회지
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    • 제21권1호
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    • pp.117-125
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    • 2007
  • Neuronal ischemia is a pathological process caused by a lack of oxygen (anoxia) and glucose (hypoglycemia), resulting in neuronal death. It is believed that apoptosis is one of the mechanisms involved in ischemic cell death. Neuronal apoptosis is a process characterized by nuclear DNA fragmentation, changes of plasma membrane organization. To elucidate the mechanism of neuronal death following ischemic insult and to develop neuroprotective effects of Daebowonjeon(DBWJ) against ischemic damage, in vitro models are used. In vitro models of cell death have been devloped with pheochromocytoma (PC12) cell, which have become widely used as neuronal models of oxidative stress, trophic factor, serum deprivation and chemical hypoxia. Using a special ischemic device and PC12 cultures, we investigated an in vitro model of ischemia based on combined Oxygen and Glucose Deprivation (OGD) insult, followed by reoxygenation, mimicking the pathological conditions of ischemia. In this study, Daebowonjeon rescued PC12 cells from Oxygen-Glucose Deprivation (OGD)-induced cell death in a dose-dependent manner The nuclear staining of PC12 cells clearly showed that DBWJ attenuated nuclear condensation and fragmentation which represent typical neuronal apoptotic characteristics. DBWJ also prevents the LDH release and induction of Hypoxia Inducing Factor (HIF)-1 by OGD-exposed PC12 cells. Furthermore, DBWJ reduced the activation of polyADP-ribose polymerase (PARP) by OGO-exposed PC12 cells. These results suggest that apoptosis is an important characteristic of OGD-induced neuronal death and that oriental medicine, such as DBWJ, may prevent PC12 cell from OG D-induced neuronal death by inhibiting the apoptotic process.

수온 및 염분 스트레스에 따 른 참담치, Mytilus coruscus에서 Hsp70 및 GST 유전자 발현에 대한 연구 (The Expression of Hsp70 and GST Genes in Mytilus coruscus Exposed to Water Temperature and Salinity)

  • 김철원;강한승
    • 환경생물
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    • 제33권4호
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    • pp.450-458
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    • 2015
  • The heat shock proteins (Hsps), one of the most highly conserved groups of proteins, play crucial roles in protecting cells against environmental stressors, such as temperature, salinity, heavy metals and pathogenic bacteria. The glutathione S-transferases (GST) have important role in detoxification of oxidative damage, environmental chemicals and environmental stress. The purpose of this study is to investigate the gene expression of Hsp70 and GST on change of temperature and salinity in Mytilus coruscus. The M. coruscus was cultured in incubator of separate temperature and salinity (8, 20, $30^{\circ}C{\times}20$‰, 25‰, 30‰) for 28 days. Ten individuals in each group were selected after each 14 and 28 days exposure. Results that the expression of Hsp70 mRNA was no significant changed in M. coruscus exposed to temperature ($8^{\circ}C$, $20^{\circ}C$, $30^{\circ}C$) and salinity (20‰, 25‰, 30‰) for 14 days. Whereas the expression of Hsp70 mRNA was increased in exposure to temperature $30^{\circ}C$ and salinity (20‰, 25‰, 30‰) for 28 days. The expression of GST mRNA was increased in exposure to temperature $30^{\circ}C$, salinity (25‰, 30‰) for 14 days and temperature ($8^{\circ}C$, $20^{\circ}C$, $30^{\circ}C$), salinity (20‰, 25‰, 30‰) for 28 days. These results suggest that Hsp70 and GST were played roles in biomarker gene on the thermal and salinity stress.

Deletion of GSTM1 and T1 Genes as a Risk Factor for Development of Acute Leukemia

  • Dunna, Nageswara Rao;Vure, Sugunakar;Sailaja, K.;Surekha, D.;Raghunadharao, D.;Rajappa, Senthil;Vishnupriya, S.
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권4호
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    • pp.2221-2224
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    • 2013
  • The glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of a wide range of chemicals, including important environmental carcinogens, as well as chemotherapeutic agents. In the present study 294 acute leukemia cases, comprising 152 of acute lymphocytic leukemia (ALL) and 142 of acute myeloid leukemia, and 251 control samples were analyzed for GSTM1 and GSTT1 polymorphisms through multiplex PCR methods. Significantly increased frequencies of GSTM1 null genotype (M0), GSTT1 null genotype (T0) and GST double null genotype (T0M0) were observed in the both ALL and AML cases as compared to controls. When data were analyzed with respect to clinical variables, increased mean levels of WBC, Blast %, LDH and significant reduction in DFS were observed in both ALL and AML cases with T0 genotype. In conclusion, absence of both GST M & GST T might confer increased risk of developing ALL or AML. The absence of GST enzyme might lead to oxidative stress and subsequent DNA damage resulting in genomic instability, a hallmark of acute leukemia. The GST enzyme deficiency might also exert impact on clinical prognosis leading to poorer DFS. Hence GST genotyping can be made mandatory in management of acute leukemia so that more aggressive therapy such as allogenic stem cell transplantation may be planned in the case of patients with a null genotype.

Effect of Genistein on Antioxidative Defence System and Membrane Fluidity in Chick Skeletal Muscle Cells

  • Jiang, Z.Y.;Jiang, S.Q.;Lin, Y.C.;Ma, X.Y.;Xi, P.B.;Cao, T.;Wang, X.Q.
    • Asian-Australasian Journal of Animal Sciences
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    • 제21권8호
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    • pp.1220-1225
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    • 2008
  • This study was conducted to investigate the protective effect of genistein on the antioxidative defence system and membrane fluidity in chick skeletal muscle cells after supplementation with 0, 20, 40, and $80{\mu}mol/L$ genistein in $50{\mu}mol/L$ $FeSO_4/H_2O_2$ treated cells for 24 h. Genistein supplementation recovered the decreased activity of total superoxide dismutase induced by $FeSO_4/H_2O_2$, significantly increased glutathione peroxidase activity (p<0.05) and decreased malondialdehyde production (p<0.05). The treatment of 80 mol/L genistein in $FeSO_4/H_2O_2$ treated cells decreased the secretion of creatine kinase (p<0.05). Fluorescence polarization values and microviscosities observed with $FeSO_4/H_2O_2$ treated cells were significantly higher than those observed with no $FeSO_4/H_2O_2$ treated cells. The addition of $80{\mu}mol/L$ genistein improved the increased fluorescence polarization value (p<0.05) caused by $FeSO_4/H_2O_2$ treatment. The microviscosity value was significantly decreased by adding genistein (p<0.05). In conclusion, genistein protected skeletal muscle cells from oxidative damage by improving antioxidative status and membrane fluidity.

The Effects of Dietary Turkish Propolis and Vitamin C on Performance, Digestibility, Egg Production and Egg Quality in Laying Hens under Different Environmental Temperatures

  • Seven, Pinar Tatli
    • Asian-Australasian Journal of Animal Sciences
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    • 제21권8호
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    • pp.1164-1170
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    • 2008
  • In this study, the effects of propolis and vitamin C (L-ascorbic acid) supplementation in diets were investigated on feed intake (FI), body weight (BW), body weight gain (BWG), feed conversion rate (FCR) and digestibility and on egg production and qualities (weight, mortality, shell thickness) in laying hens exposed to heat stress. A total of 150 Hyline White Leghorn, aged 42 weeks, hens was divided into five groups of 30 hens. Chicks were randomly divided into 1 positive control, 1 control and 3 treatment groups. The chicks were kept in cages in temperature-controlled rooms at $22^{\circ}C$ for 24 h/d (positive control, Thermoneutral, TN group) or $34^{\circ}C$ for 9 h/d from 08.00-17.00 h followed by $22^{\circ}C$ for 15 h (control, heat stress, HS group) and fed a basal diet or basal diet supplemented with vitamin C (250 mg/kg of L- ascorbic acid/kg of diet) or two levels of propolis (2 and 5 g of ethanol extracted propolis/kg of diet). Increased FI (p<0.05) and improvement in FCR (p<0.05), hen day egg (p<0.05) and egg weight (p<0.05) were found in Vitamin C and propolis-supplemented laying hens reared under heat stress conditions. Mortality rate was higher in the control group than TN, vitamin C and propolis groups (p<0.05). Digestibility of dry matter, organic matter, crude protein and ether extract improved with increasing of both dietary vitamin C and propolis (p<0.05). Vitamin C or propolis supplementation did not affect either the percentage shape index, yolk index or haugh unit and albumen index (p>0.05). However, the egg shell thickness and egg shell weight appeared to be increased in Vitamin C and propolis groups in comparison to HS group birds (p<0.05). In conclusion, dietary supplementation of laying hens with anti-oxidants (vitamin C and propolis) can attenuate heat stress-induced oxidative damage. These positive effects were evidenced by increased growth performance and digestibility, improvement of egg shell thickness and egg weight in comparison to non-supplemented birds. Moreover, supplementation with propolis (5 g/kg diet) was the most efficient treatment.

The Effect of Melatonin on Mitochondrial Function in Endotoxemia Induced by Lipopolysaccharide

  • Liu, Jing;Wu, Fengming;Liu, Yuqing;Zhang, Tao;Tang, Zhaoxin
    • Asian-Australasian Journal of Animal Sciences
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    • 제24권6호
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    • pp.857-866
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    • 2011
  • This study examined the metabolism of free radicals in hepatic mitochondria of goats induced by lipopolysaccharide (LPS), and investigated the effects of melatonin (MT). Forty-eight healthy goats ($10{\pm}1.2\;kg$) were randomly selected and divided into four groups: saline control, LPS, MT+LPS and MT. The goats within each group were3 sacrificed either 3 or 6 h after treatment and the livers removed to isolate mitochondria. The respiration control ratio (RCR), the ADP:O ratio, the oxidative phosphorylation ratio (OPR), the concentration of $H_2O_2$ and the activities of Complex I-IV were determined. The mitochondrial membrane potential ($\Delta\psi_m$) was analyzed by flow cytometry. The results showed that RCR, O/P and OPR of the LPS group decreased (p<0.05), as well as activities of respiratory complexes, whereas the generation of $H_2O_2$ in Complex III increased (p<0.05) after 3 h, while Complex II and III increased after 6 h. Also, it was found that the mitochondrial membrane potential of the LPS group declined (p<0.05). However, pre-treatment with MT attenuated the injury induced by LPS, which not only presented higher (p<0.05) RCR, O/P, OPR, and respiratory complex activities, but also maintained the $\Delta\psi_m$. Interestingly, it is revealed that, in the MT+LPS group, the generation of $H_2O_2$ increased firstly in 3 h, and then significantly (p<0.05).decreased after 6 h. In the MT group, the function of mitochondria, the transmenbrane potential and the generation of $H_2O_2$ were obviously improved compared to the control group. Conclusion: melatonin prevents damage caused by LPS on hepatic mitochondria of goats.

Allithiamine Exerts Therapeutic Effects on Sepsis by Modulating Metabolic Flux during Dendritic Cell Activation

  • Choi, Eun Jung;Jeon, Chang Hyun;Park, Dong Ho;Kwon, Tae-Hwan
    • Molecules and Cells
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    • 제43권11호
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    • pp.964-973
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    • 2020
  • Recent studies have highlighted that early enhancement of the glycolytic pathway is a mode of maintaining the proinflammatory status of immune cells. Thiamine, a wellknown co-activator of pyruvate dehydrogenase complex, a gatekeeping enzyme, shifts energy utilization of glucose from glycolysis to oxidative phosphorylation. Thus, we hypothesized that thiamine may modulate inflammation by alleviating metabolic shifts during immune cell activation. First, using allithiamine, which showed the most potent anti-inflammatory capacity among thiamine derivatives, we confirmed the inhibitory effects of allithiamine on the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and maturation process in dendritic cells. We applied the LPS-induced sepsis model to examine whether allithiamine has a protective role in hyper-inflammatory status. We observed that allithiamine attenuated tissue damage and organ dysfunction during endotoxemia, even when the treatment was given after the early cytokine release. We assessed the changes in glucose metabolites during LPS-induced dendritic cell activation and found that allithiamine significantly inhibited glucose-driven citrate accumulation. We then examined the clinical implication of regulating metabolites during sepsis by performing a tail bleeding assay upon allithiamine treatment, which expands its capacity to hamper the coagulation process. Finally, we confirmed that the role of allithiamine in metabolic regulation is critical in exerting anti-inflammatory action by demonstrating its inhibitory effect upon mitochondrial citrate transporter activity. In conclusion, thiamine could be used as an alternative approach for controlling the immune response in patients with sepsis.

현호소약침액(玄胡索藥鍼液)의 acetylcholinesterase 억제효과와 항산화에 미치는 영향(影響) (Effect of Corydalis tuber Acua-acupuncture Solution on Antiacetylcholinesterase and Antioxidants)

  • 강미경;남상수;이윤호
    • Journal of Acupuncture Research
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    • 제21권3호
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    • pp.235-248
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    • 2004
  • It has been investigated about aging theory. However, aging mechanism still remains to be unknown. Aging and aging related diseases might be due to oxidative damage and these were modifiable by genetic and environmental factors. For designing an optimal medical treatment and countermeasure against aging and aging related disease, it is necessary to understand the aging mechanism. Acetylcholine(Ach) plays an important role in memory. If someone doesn't have enough Ach, he has a tendency to catch a Alzheimer's disease. Corydalis tuber has been clinically used to treat heart disease, gastrointestinal disease and other diseases including endocrine disease in Oriental medicine. The purpose of this article is to investigate the inhibitory effect on Acetylcholinesterase and scavenging effects on NO, DPPH of Corydalis tuber Acua-acupuncture solution(CTAS). The results are summerised as follows; 1. There is a significant inhibitory effect of $0.01mg/m{\ell}$ CTAS group at 20, 30, 60 minutes and $0.1mg/m{\ell}$ CTAS group at 10, 20, 30, 60 minutes on AchE. 2. There is no significant scavenging effect of CTAS on NO. 3. There is a significant scavenging effect of $0.1mg/m{\ell}$ and $0.01mg/m{\ell}$ CTAS group at 10 minutes but there is no significant scavenging effect at 20, 30, 60 minutes on DPPH. There is a significant scavenging effect of $1mg/m{\ell}$ CTAS group at 10, 20, 30, 60 minutes on DPPH.

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Evaluating the Influence of Side Stream Cigarette Smoke at an Early Stage of Non-Alcoholic Steatohepatitis Progression in Mice

  • Kim, Jong Won;Yun, Hyejin;Choi, Seong-Jin;Lee, Sang-Hyub;Park, Surim;Lim, Chae Woong;Lee, Kyuhong;Kim, Bumseok
    • Toxicological Research
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    • 제33권1호
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    • pp.31-41
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    • 2017
  • Side stream cigarette smoke (SSCS) is known to be as harmful and hazardous to human health as is active smoking. In this study, we investigated the relationship between the exposure to SSCS and its stimulatory and subacute effects on the progression of non-alcoholic steatohepatitis (NASH). A methionine and choline-deficient plus high fat (MCDHF) diet was administered to C57BL/6 mice for 6 weeks. During the first three weeks of MCDHF diet feeding, each diet group was exposed to SSCS (0, 20, $40{\mu}g/L$) or fresh air for 2 hrs per day and 5 days per week. Additional experiments were performed by increasing the concentration (0, 30, $60{\mu}g/L$) and exposure time (6 hours per day) of SSCS. According to histopathologic analysis and serum levels of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), there were no differences in hepatic fat deposition, fibrosis, apoptosis or liver damage in MCDHF-fed mice based on SSCS exposure. There were also no differences in the expression of inflammation-, oxidative stress- or fibrosis-related genes between MCDHF-fed mice with or without SSCS exposure. Therefore, it is concluded that SSCS with current exposure amounts does not have additive detrimental effects on the early stage of NASH.