Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions (穀胱甘肽相關的物質可以在缺氧的情況下維持心肌細胞的收縮功能)

Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions

穀胱甘肽相關的物質可以在缺氧的情況下維持心肌細胞的收縮功能

Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions (穀胱甘肽相關的物質可以在缺氧的情況下維持心肌細胞的收縮功能)

穀胱甘肽相關的物質可以在缺氧的情況下維持心肌細胞的收縮功能 (Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions)

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Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions; PY2019; Russian Academy of Sciences, Russia (俄羅斯);_WJD_2019-1020_V001R01_IR94_RvD20191020_

Source (資訊來源):

https://www.nature.com/articles/s41598-019-41266-2

Info cited on 2019-10-20-WD7 (資訊引用於 中華民國108年10月20日) by 湯偉晉 (WeiJin Tang)

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【Title of Professional Medical Paper (專業醫學論文的標題)】, 【English sentence or text translated by WeiJin Tang (湯偉晉翻譯的英文句子或文字)】, 

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Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients

2019-09-26

Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients

Source (資訊來源):

https://www.nature.com/articles/mp201488

Info cited on 2019-09-26-WD4 (資訊引用於 中華民國108年9月26日) by 湯偉晉 (WeiJin Tang)

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integrity, glutathione

integrity, glutathione

Source (資訊來源):

https://www.google.com/search?q=integrity%2C+glutathione&oq=integrity%2C+glutathione&aqs=chrome..69i57j69i65l3.3561j1j4&sourceid=chrome&ie=UTF-8

Info cited on 2019-09-26-WD4 (資訊引用於 中華民國108年9月26日) by 湯偉晉 (WeiJin Tang)

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Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function; PY2018; Spain (西班牙);_WJD_2019-0926_V001R01_IR94_RvD20190926_

2019-09-26

Hippocampal neurons require a large pool of glutathione to sustain dendrite integrity and cognitive function; PY2018; Spain (西班牙);_WJD_2019-0926_V001R01_IR94_RvD20190926_

Source (資訊來源):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092450/

Info cited on 2019-09-26-WD4 (資訊引用於 中華民國108年9月26日) by 湯偉晉 (WeiJin Tang)

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Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells [2004](IR92) 01.png

Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells PY2004 IR94

Source (資訊來源):

https://www.ncbi.nlm.nih.gov/pubmed/15126641

Info cited on 2019-09-26-WD4 (資訊引用於 中華民國108年9月26日) by 湯偉晉 (WeiJin Tang)

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Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells [2004](IR92) 01.png

Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells [2004](IR92) 02.png

Superoxide Dismutase in Redox Biology - The roles of superoxide and hydrogen peroxide [2011](IR93) - Ascorbate is the terminal, water-soluble, small-molecule antioxidant.png

Superoxide Dismutase in Redox Biology - The roles of superoxide and hydrogen peroxide [2011](IR93).png

Signal transduction by reactive oxygen species; PY2011;National Institutes of Health, USA (美國);_WJD_2019-0903_V001R01_IR94_RvD20190903_IR95_

Signal transduction by reactive oxygen species; PY2011;National Institutes of Health, USA (美國);_WJD_2019-0903_V001R01_IR94_RvD20190903_IR95_

Signal transduction by reactive oxygen species; PY2011;National Institutes of Health, USA (美國);_WJD_2019-0903_V001R01_IR94_RvD20190903_IR95_

Source (資訊來源):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135394/

Info cited on 2019-09-03-WD2 (資訊引用於 中華民國108年9月3日) by 湯偉晉 (WeiJin Tang)

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Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.; PY1988;Thomas Jefferson University, USA (美國);_WJD_2019-0902_V001R01_IR94_

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2019-09-02

Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.; PY1988;Thomas Jefferson University, USA (美國);_WJD_2019-0902_V001R01_IR94_RvD20190902_

Source (資訊來源):

https://www.ncbi.nlm.nih.gov/pubmed/3421709

Info cited on 2019-09-02-WD1 (資訊引用於 中華民國108年9月2日) by 湯偉晉 (WeiJin Tang)

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Arch Biochem Biophys. 1988 Sep;265(2):311-20.

Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.

Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.

Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.

Miccadei S1, Kyle ME, Gilfor D, Farber JL.

Author information

1

Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

Thomas Jefferson University, USA (美國)

Abstract

Cultured hepatocytes were exposed to two chemicals, dinitrofluorobenzene (DNFB) and diethyl maleate (DEM), that abruptly deplete cellular stores of glutathione (穀胱甘肽). Upon the loss of GSH, lipid peroxidation was evidenced by an accumulation of malondialdehyde in the cultures followed by the death of the hepatocytes. Pretreatment of the hepatocytes with a ferric iron chelator, deferoxamine, or the addition of an antioxidant, N,N'-diphenyl-p-phenylenediamine (DPPD), to the culture medium prevented both the lipid peroxidation and the cell death produced by either DNFB or DEM. However, neither deferoxamine nor DPPD prevented the depletion of GSH caused by either agent. Inhibition of glutathione (穀胱甘肽) reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or inhibition of catalase by aminotriazole sensitized the hepatocytes to the cytotoxicity of DNFB. In a similar manner, pretreatment with BCNU potentiated the cell killing by DEM. DPPD and deferoxamine protected hepatocytes pretreated with BCNU and then exposed to DNFB or DEM. These data indicate that an abrupt depletion of GSH leads to lipid peroxidation and cell death in cultured hepatocytes. It is proposed that GSH depletion sensitizes the hepatocyte to its constitutive flux of partially reduced oxygen species. Such an oxidative stress is normally detoxified by GSH-dependent mechanisms. However, with GSH depletion these activated oxygen species are toxic as a result of the iron-dependent formation of a potent oxidizing species.

Begin_電腦自動翻譯的內容_Y2019m09d02h15m08Rn0660_

(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)

抽象

將培養的肝細胞暴露於兩種化學物質，即二硝基氟苯（DNFB）和馬來酸二乙酯（DEM），其突然耗盡穀胱甘肽的細胞儲存。在GSH喪失後，脂質過氧化通過培養物中丙二醛的積累隨後肝細胞的死亡得到證實。用鐵螯合劑，去鐵胺或添加抗氧化劑N，N'-二苯基 - 對苯二胺（DPPD）預處理肝細胞，防止DNFB產生的脂質過氧化和細胞死亡或DEM。然而，去鐵胺和DPPD均未阻止任何一種藥物引起的GSH耗竭。 1,3-雙（2-氯乙基）-1-亞硝基脲（BCNU）對穀胱甘肽還原酶的抑製或氨基三唑對過氧化氫酶的抑制使肝細胞對DNFB的細胞毒性敏感。以類似的方式，用BCNU預處理增強了DEM對細胞的殺傷作用。 DPPD和去鐵胺保護用BCNU預處理的肝細胞，然後暴露於DNFB或DEM。這些數據表明GSH的突然耗盡導致培養的肝細胞中的脂質過氧化和細胞死亡。提出GSH耗竭使肝細胞對其部分還原的氧物種的組成型通量敏感。這種氧化應激通常通過GSH依賴性機制解毒。然而，隨著GSH耗盡，這些活化的氧物質由於鐵依賴性形成有效的氧化物質而具有毒性。

End_電腦自動翻譯的內容_Y2019m09d02h15m08Rn0660_

PMID: 3421709 DOI: 10.1016/0003-9861(88)90133-6

[Indexed for MEDLINE]

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Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review.; PY2016;Maharshi Dayanand University, India (印度);_WJD_2019-0902_

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2019-09-02

Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review.; PY2016;Maharshi Dayanand University, India (印度);_WJD_2019-0902_V001R01_IR92_RvD20190902_

Source (資訊來源):

https://www.ncbi.nlm.nih.gov/pubmed/26510484

Info cited on 2019-09-02-WD1 (資訊引用於 中華民國108年9月2日) by 湯偉晉 (WeiJin Tang)

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J Appl Toxicol. 2016 Feb;36(2):179-88. doi: 10.1002/jat.3256. Epub 2015 Oct 29.

Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review.

Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review.

Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review.

Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review.

Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review.

Prakash C1, Soni M1, Kumar V1.

Author information

1

Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124001, Haryana, India.

Abstract

Arsenic is a toxic metalloid present ubiquitously on earth. Since the last decade, it has gained considerable attention due to its severe neurotoxic effects. Arsenic can cross the blood-brain barrier and accumulate in different regions of the brain suggesting its role in neurological diseases. Arsenic exposure has been associated with reactive oxygen species generation, which is supposed to be one of the mechanisms of arsenic-induced oxidative stress. Mitochondria, being the major source of reactive oxygen species generation may present an important target of arsenic toxicity. It is speculated that the proper functioning of the brain depends largely on efficient mitochondrial functions. Multiple studies have reported evidence of brain mitochondrial impairment after arsenic exposure. In this review, we have evaluated the proposed mechanisms of arsenic-induced mitochondrial oxidative stress and dysfunction. The understanding of molecular mechanism of mitochondrial dysfunction may be helpful to develop therapeutic strategies against arsenic-induced neurotoxicity. The ameliorative measures undertaken in arsenic-induced mitochondrial dysfunction have also been highlighted.

Copyright © 2015 John Wiley & Sons, Ltd.

KEYWORDS:

arsenic; membrane potential; mitochondrial dysfunction; neurotoxicity; oxidative stress

PMID: 26510484 DOI: 10.1002/jat.3256

[Indexed for MEDLINE]

KEYWORDS added by WeiJin Tang:

Glutathione, cysteine

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Changes in certain hematological and physiological variables following single gallium arsenide exposure in rats.; PY1997;Defense Research & Development Establishment, Gwalior, India (印度);_WJD_2019-0902_

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2019-09-02

Changes in certain hematological and physiological variables following single gallium arsenide exposure in rats.; PY1997;Defense Research & Development Establishment, Gwalior, India (印度);_WJD_2019-0902_V001R01_IR92_RvD20190902_

Source (資訊來源):

https://www.ncbi.nlm.nih.gov/pubmed/9403132

Info cited on 2019-09-02-WD1 (資訊引用於 中華民國108年9月2日) by 湯偉晉 (WeiJin Tang)

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Biol Trace Elem Res. 1997 Sep;58(3):197-208.

Changes in certain hematological and physiological variables following single gallium arsenide exposure in rats.

Changes in certain hematological and physiological variables following single gallium arsenide exposure in rats.

Changes in certain hematological and physiological variables following single gallium arsenide exposure in rats.

Flora SJ1, Dube SN, Vijayaraghavan R, Pant SC.

Author information

1

Division of Pharmacology and Toxicology, Defense Research & Development Establishment, Gwalior, India.

Abstract

Gallium arsenide (GaAs), a group III-VA intermetallic semiconductor, possesses superior electronic and optical properties and has a wide application in electronic industry. Exposure to GaAs in the semiconductor industries could be a possible occupational risk. The aim of the present study was to determine the dose-dependent effect of single oral exposure to GaAs (500, 1000, or 2000 mg/kg) on some biochemical variables in heme synthesis pathway and few selected physiological variables at d 1, 7, and 15 following administration. The results indicate that GaAs produced a significant effect on the activity of delta-aminolevulinic acid dehydratase (ALAD) in blood and heart (particularly at d 7) following exposure to 2000 mg/kg, whereas urinary delta-aminolevulinic acid (ALA) excretion was elevated only at d 7. No marked influence of GaAs on blood hemoglobin, zinc protoporphyrin, and packed cell volume was noticed. Blood glutathione (GSH) was significantly reduced at d 7, but remained unchanged at two other time intervals. On the other hand, heart GSH contents remained uninfluenced on GaAs exposure. Most of the physiological variables, viz. blood pressure, heart and respiration rate, and twitch response, remained unchanged, except for some minor alterations observed at d 7 and 15 following exposure to GaAs at a dose of 2000 mg/kg. Blood gallium concentration was not detectable in normal animals and rats exposed to 500 mg/kg GaAs. Blood arsenic concentration was, however, detectable even at the a lower dose level and increased in a dose-dependent manner. All these changes showed a recovery pattern at d 21, indicating that the alterations are reversible.

PMID: 9403132

[Indexed for MEDLINE]

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Scientist Meng-Er Huang; Institut Curie (IC) is a private nonprofit organization created in 1909 which combines a leading European cancer research center;_WJD_2019-0721_

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2019-07-21
Scientist Meng-Er Huang; Institut Curie (IC) is a private nonprofit organization created in 1909 which combines a leading European cancer research center;_WJD_2019-0721_V001R01_IR94_RvD20190721_

Source (資訊來源):
https://science.institut-curie.org/research/biology-chemistry-of-radiations-cell-signaling-and-cancer-axis/umr3348-genotoxic-stress-and-cancer/equipe-huang/
Info cited on 2019-07-21-WD7 (資訊引用於 中華民國108年7月21日) by 湯偉晉 (WeiJin Tang)
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Source (資訊來源):
https://science.institut-curie.org/research/biology-chemistry-of-radiations-cell-signaling-and-cancer-axis/umr3348-genotoxic-stress-and-cancer/equipe-huang/team-members/?mbr=meng-er-huang-md-phd
Info cited on 2019-07-21-WD7 (資訊引用於 中華民國108年7月21日) by 湯偉晉 (WeiJin Tang)
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OXIDATIVE STRESS, REDOX REGULATION AND CELL FATE
PARTAGER

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Huang
Meng-Er Huang
Team Leader
meng-er.huang@curie.fr
Tel: +33 (0)1 69 86 30 16

Reactive oxygen species (ROS) and dynamic intracellular reductive/oxidative (redox) balance are critical for normal cellular functions. Disruption of redox homeostasis leads to aberrant cell signaling, macromolecules damage and is associated with human pathologies such as neuro-degenerative diseases and cancers.

Our team has been conducting research to better understand redox regulation, oxidative stress response mechanisms, and ROS induced genome instability and cell death. We use two complementary experimental systems, human cell lines and the yeast S. cerevisiae to investigate these mechanisms.

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Figure 1: Schematic illustration of cellular redox homeostasis. Major reactive oxygen species (ROS) and antioxidant elements are indicated (upper panel). SOD, superoxide dismutases; PRX, peroxiredoxins; TRX, thioredoxins; GRX, glutaredoxins; GPX, glutathione peroxidases; GSH, glutathione. ROS are involved in cell signalling, whereas a severe and prolonged increase of ROS cause oxidative stress (lower panel).
Our current research activities focus on the following projects. The project I is to study the biological function of oxidative stress response system (Figure 1), including peroxiredoxins, thioredoxins and glutathione regarding genome stability maintenance and cell death regulation in yeast and in human cells. These elements are not only the first line of defence against deleterious effect of oxidative stress but also actively involved in redox signaling. More recently, we focused our effort on characterizing the subcellular compartments redox environments and their dynamic regulations in various biological processes (Figure 2). The project II is to understand the physiological role of the S. cerevisiae protein complex Tah18/Dre2 and to define its biochemical properties. This protein complex exhibits functional interaction with the DNA polymerase delta and may be implicated in linking intracellular redox states to cell fate. We wish to understand more precisely how this complex is linked to DNA replication via iron-sulfur (Fe-S) biosynthesis. The project III aims to exploits redox-modulating strategies as a therapeutic approach. Therapeutic selectivity in cancer therapy could be achieved by ROS-mediated mechanisms based on the different redox states in normal and malignant cells. We are studying whether and how a rational redox modulation could have selective and synergistic effects together with treatment by drugs or ionizing radiations in cancer cells.

Figure 2: Adressage de sondes rédox fluorescentes (rxYFP) dans les compartiments cytosolique, nucléaire et mitochondrial (matrice) de cellules HeLa (panneau supérieur). Analyse au cours du temps des changements rédox au sein des différents compartiments cellulaires, en réponse à un traitement par H2O2 (panneau inférieur).
Figure 2: Targeting a yellow fluorescent protein-based redox sensor (rxYFP) to the cytosol, nucleus and mitochondrial matrix of HeLa cells (upper panel) and time course analysis of compartment-specific redox changes in response to H2O2 treatments (lower panel).
Key publications
Year of publication 2018
Elie Hatem, Sandy Azzi, Nadine El Banna, Tiantian He, Amélie Heneman-Masurel, Laurence Vernis, Dorothée Baïlle, Vanessa Masson, Florent Dingli, Damarys Loew, Bruno Azzarone, Pierre Eid, Giuseppe Baldacci, Meng-Er Huang (2018 Nov 20)
Auranofin/Vitamin C: A Novel Drug Combination Targeting Triple-Negative Breast Cancer.
Journal of the National Cancer Institute : DOI : 10.1093/ije/djy149
Year of publication 2017
Elie Hatem, Nadine El Banna, Meng-Er Huang (2017 Nov 20)
Multifaceted roles of glutathione and glutathione-based systems in carcinogenesis and anticancer drug resistance.
Antioxidants & redox signaling : DOI : 10.1089/ars.2017.7134
Year of publication 2016
Meng-Er Huang, Céline Facca, Zakaria Fatmi, Dorothée Baïlle, Safia Bénakli, Laurence Vernis (2016 Jul 11)
DNA replication inhibitor hydroxyurea alters Fe-S centers by producing reactive oxygen species in vivo.
Scientific reports : 29361       : DOI : 10.1038/srep29361
Year of publication 2015
Tiantian He, Elie Hatem, Laurence Vernis, Ming Lei, Meng-Er Huang (2015 Dec 21)
PRX1 knockdown potentiates vitamin K3 toxicity in cancer cells: a potential new therapeutic perspective for an old drug.
Journal of experimental & clinical cancer research : CR : 152   : DOI : 10.1186/s13046-015-0270-2
Year of publication 2014
Sandrine Ragu, Michèle Dardalhon, Sushma Sharma, Ismail Iraqui, Géraldine Buhagiar-Labarchède, Virginie Grondin, Guy Kienda, Laurence Vernis, Roland Chanet, Richard D Kolodner, Meng-Er Huang, Gérard Faye (2014 Sep 23)
Loss of the thioredoxin reductase Trr1 suppresses the genomic instability of peroxiredoxin tsa1 mutants.
PloS one : e108123     : DOI : 10.1371/journal.pone.0108123
Year of publication 2013
Agata Banach-Latapy, Tiantian He, Michèle Dardalhon, Laurence Vernis, Roland Chanet, Meng-Er Huang (2013 Dec 1)
Redox-sensitive YFP sensors for monitoring dynamic compartment-specific glutathione redox state.
Free radical biology & medicine : 436-45          : DOI : 10.1016/j.freeradbiomed.2013.07.033

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Lipid peroxidation and antioxidant status in blood of patients with uterine myoma, endometrial polypus, hyperplastic and malignant endometrium; PY2006;Vinca Institute of Nuclear Sciences;Serbia (塞爾維亞);_WJD_2019-0721_

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2019-07-21
Lipid peroxidation and antioxidant status in blood of patients with uterine myoma, endometrial polypus, hyperplastic and malignant endometrium; PY2006;Vinca Institute of Nuclear Sciences;Serbia (塞爾維亞);_WJD_2019-0721_
Source (資訊來源):
https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000500005
Info cited on 2019-07-21-WD7 (資訊引用於 中華民國108年7月21日) by 湯偉晉 (WeiJin Tang)
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Biological Research
versión impresa ISSN 0716-9760
Biol. Res. v.39 n.4 Santiago  2006
http://dx.doi.org/10.4067/S0716-97602006000500005

BiolRes 39: 619-629, 2006

Lipid peroxidation and antioxidant status in blood of patients with uterine myoma, endometrial polypus, hyperplastic and malignant endometrium

Begin_電腦自動翻譯的內容_Y2019m07d21h21m46Rn0177_
(注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
子宮肌瘤，子宮內膜息肉，增生和惡性子宮內膜患者血液中脂質過氧化和抗氧化狀態
End_電腦自動翻譯的內容_Y2019m07d21h21m46Rn0177_

SNEZANA PEJIC, JELENA KASAPOVIC, ANA TODOROVIC, VESNA STOJILJKOVIC, and SNEZANA B. PAJOVIC
Laboratory of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, Belgrade, Serbia (塞爾維亞)

ABSTRACT
Oxidative stress is considered to be involved in pathogenesis of many disorders of the female genital tract. In this study, we explored the lipid peroxidation levels and antioxidant enzyme activities in women diagnosed with different forms of uterine diseases in order to evaluate the extent of oxidative stress in blood of such patients. Blood samples of healthy subjects and gynecological patients were collected and subjected to assays for superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and lipid hydroperoxides. The results show that alterations of measured parameters vary with the enzyme type and diagnosis. However, both reduction in antioxidants and elevation of lipid peroxidation were observed in general. Lipid hydroperoxides level was negatively correlated to superoxide dismutase and glutathione peroxidase activities, as well as positively correlated to catalase activity. In addition, the lipid hydroperoxides/ glutathione peroxidase ratio was found to be increased, according to the type of uterine disease. The obtained results show that perturbation of antioxidant status is more pronounced in blood of patients with premalignant (hyperplastic) and malignant (adenocarcinoma) lesions, compared to those with benign uterine changes such as polypus and myoma.

Begin_電腦自動翻譯的內容_Y2019m07d21h21m53Rn3151_
(注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
抽象
氧化應激被認為涉及許多女性生殖道疾病的發病機理。在這項研究中，我們探討了被診斷患有不同形式子宮疾病的女性的脂質過氧化水平和抗氧化酶活性，以評估這些患者血液中氧化應激的程度。收集健康受試者和婦科患者的血液樣品，並進行超氧化物歧化酶，過氧化氫酶，穀胱甘肽過氧化物酶，穀胱甘肽還原酶和脂質氫過氧化物的測定。結果表明，測量參數的變化隨酶類型和診斷而變化。然而，通常觀察到抗氧化劑的減少和脂質過氧化的升高。脂質氫過氧化物水平與超氧化物歧化酶和穀胱甘肽過氧化物酶活性呈負相關，並且與過氧化氫酶活性呈正相關。此外，根據子宮疾病的類型，發現脂質氫過氧化物/穀胱甘肽過氧化物酶比率增加。獲得的結果表明，與具有良性子宮變化的患者（例如息肉和肌瘤）相比，具有癌前（增生）和惡性（腺癌）病變的患者的血液中抗氧化狀態的擾動更明顯。

End_電腦自動翻譯的內容_Y2019m07d21h21m53Rn3151_

Key terms: antioxidant enzymes, endometrial polypus, endometrial hyperplasia, endometrial adenocarcinoma, lipid peroxidation, uterine myoma,

INTRODUCTION

It is widely accepted that excess production of free radicals, particularly oxygen radicals, creates a condition known as oxidative stress, which causes cell damage and plays fundamental role in various diseases, aging and neoplastic transformation (Sun, 1990; Halliwell, 1996). Also, by-products of lipid peroxidation perturb structural organization and functions of the cell membrane, consequently leading to cell destruction (Porter et al., 1995; Spiteller, 2003). Deleterious effects of reactive oxygen species (ROS) and lipid peroxidation (LPO) products are counteracted by the antioxidative defense system (AOS), which consists of nonenzymatic antioxidant molecules such as tocopherol, carotenoids, ascorbate, glutathione (Briviba and Sies, 1994) and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reducíase (GR), and glutathione transferase (GST). SOD, the first line of defense against oxygen free radicals, catalyzes dismutation of superoxide anion radical into hydrogen peroxide (H202), which can be transformed into water and oxygen by CAT or GPx. Besides hydrogen peroxide, GPx also reduces lipid or nonlipid hydroperoxides while oxidizing glutathione (GSH). The oxidized GSH is then reduced by GR (Yu, 1994). Antioxidants show different patterns during neoplastic transformation and tumor cells exhibit high variability of antioxidant enzymes (AOE) activities, when compared to their appropriate normal cell counterparts (Sun, 1990).

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介紹

人們普遍認為，過量產生的自由基，尤其是氧自由基，會產生一種稱為氧化應激的狀態，這種狀況會導致細胞損傷，並在各種疾病，衰老和腫瘤轉化過程中發揮重要作用（Sun，1990; Halliwell，1996）。此外，脂質過氧化的副產物擾亂細胞膜的結構組織和功能，從而導致細胞破壞（Porter等，1995; Spiteller，2003）。抗氧化防禦系統（AOS）抵消了活性氧（ROS）和脂質過氧化（LPO）產物的有害影響，其由非酶抗氧化分子如生育酚，類胡蘿蔔素，抗壞血酸，穀胱甘肽（Briviba和Sies，1994）和抗氧化酶超氧化物歧化酶（SOD），過氧化氫酶（CAT），穀胱甘肽過氧化物酶（GPx），穀胱甘肽還原酶（GR）和穀胱甘肽轉移酶（GST）。 SOD是抗氧自由基的第一道防線，催化超氧陰離子自由基歧化成過氧化氫（H2O2），可通過CAT或GPx轉化為水和氧。除過氧化氫外，GPx還可以還原脂質或非脂質氫過氧化物，同時氧化穀胱甘肽（GSH）。然後通過GR還原氧化的GSH（Yu，1994）。抗氧化劑在腫瘤轉化過程中表現出不同的模式，與其適當的正常細胞對應物相比，腫瘤細胞表現出高度的抗氧化酶（AOE）活性變異性（Sun，1990）。

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Although endometrial hyperplasia is regarded as a preliminary stage of endometrioid carcinomas (Hammond and Johnson, 2004), there is a lack of data on the relationship between oxidative stress and antioxidant enzymes in such patients. Some investigations so far have revealed elevated levels of lipid peroxidation and perturbed AOE activities in peripheral circulation and tissues of women with benign and malign diagnosis. Chiou and Hu (1999) reported lowered plasma and erythrocytes SOD activity of both uterine cervicitis and myoma patients, while the activities of CAT and GPx were elevated in cervicitis patients and lowered in myoma patients. Similar observations on erythrocytes SOD, CAT and GPx activities of cervicitis patients were made by Manoharan et al. (2004), whereas activities of examined enzymes decreased in cervical cancer patients. Previous results of Kolanjiappan et al. (2002) and Manoharan et al. (2002) also demonstrated an elevated level of lipid peroxidation, lowered concentrations of GSH, vitamin E and CAT, disturbed antioxidant status as well as altered Na+K+-ATPase activity in erythrocytes of cervical cancer patients.

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儘管子宮內膜增生被認為是子宮內膜樣癌的初級階段（Hammond和Johnson，2004），但缺乏關於此類患者氧化應激與抗氧化酶之間關係的數據。迄今為止的一些研究表明，良性和惡性診斷的女性外周血和組織中脂質過氧化水平升高，AOE活性受到干擾。 Chiou和Hu（1999）報導了降低子宮頸炎和肌瘤患者的血漿和紅細胞SOD活性，而CAT和GPx的活性在宮頸炎患者中升高，在肌瘤患者中降低。 Manoharan等人對宮頸炎患者的紅細胞SOD，CAT和GPx活性進行了類似的觀察。 （2004），而宮頸癌患者檢查酶的活性下降。以前的結果Kolanjiappan等。 （2002年）和Manoharan等人。 （2002）也證實了宮頸癌患者紅細胞中脂質過氧化水平升高，GSH，維生素E和CAT濃度降低，抗氧化狀態受到干擾以及Na + K + -ATP酶活性改變。

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DISCUSSION

Evidence indicates that free radical species and their derivatives are the key denominators in a number of pathological conditions, including carcinogenesis (Maeda and Akaike, 1998). Although it is not clear whether oxidative stress and tumor result from an increased oxidant production or from a failure of antioxidant defense system (Toyokuni et al., 1995), impairment of the AOS is considered to be critically involved in such conditions. In neoplastic transformation, antioxidant enzyme activities have shown different patterns and they are highly variable in tissues and blood of patients with different types of cancer (Ahmed et al., 1999; Hristozov et al., 2001; Abiaka et al., 2002). This study indicates that antioxidant defense mechanisms are impaired in human uterine diseases and it also points to elevated levels of lipid peroxidation products, as markers of oxidative stress, in plasma of such patients. Namely, higher levels of LOOH as well as the LOOH/GPx ratio were recorded in all examined groups over those in controls, except for patients with polypus endometrii. The observed changes are in accordance with other findings where elevated lipid peroxidation was reported for patients with uterine cervicitis or myoma (Chiou and Hu, 1999) or cancer patients (Manju et al., 2002; Kolanjiappan et al., 2002). We also observed that circulating levels of lipid hydroperoxides and LOOH/GPx ratio are generally higher in subjects with either form of hyperplasia or adenocarcinoma than those found in polypus or myoma patients. Oxygen radical production, which elevates lipid peroxidation, increases with clinical progression of diseases (Bagchi and Puri, 1998; Skrzydlewska et al., 2005). Since patients with either form of hyperplasia or adenocarcinoma have 2.5-3.11-fold and 1.35-1.65-fold increase in the LOOH/GPx ratio compared to polypus or myoma subjects, respectively, this might indicate that such patients potentially have wider extent of cellular membrane alterations (van Ginkel and Sevanian, 1994) or DNA damage (Toyokuni, 1998). The increase in LOOH may also be due to the impaired antioxidant system as observed in the previous studies (Hristozov et al., 2001; Manoharan et al., 2004).

Superoxide dismutase, a scavenger of superoxide anions, along with catalase and glutathione peroxidase, the preventive antioxidants, play a very important role in protection against lipid peroxidation. In this study, SOD activities were lower in blood of all examined patient groups than in healthy subjects. Besides, decrease of SOD activity was much more pronounced in hyperplasia or adenocarcinoma patients than in subjects with polypus or myoma, thus making those individuals more vulnerable to oxidative stress. Decreased SOD activity in plasma of gynecological patients was also reported by Bhuvaraharamurthy et al. (1996), Chiou and Hu (1999), Manoharan et al. (2004). Reduction of SOD activity may be due to an increased endogenous production of ROS as evidenced by increased lipid hydroperoxides. In support of this observation, plasma LOOH were found to be negatively correlated with SOD activities in the examined patients.

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超氧化物歧化酶，一種超氧陰離子清除劑，以及過氧化氫酶和穀胱甘肽過氧化物酶，預防性抗氧化劑，在防止脂質過氧化反應中起著非常重要的作用。 在該研究中，所有檢查患者組的血液中SOD活性低於健康受試者。 此外，增生或腺癌患者的SOD活性降低比患有息肉或肌瘤的患者更明顯，從而使這些個體更容易受到氧化應激。 Bhuvaraharamurthy等報導了婦科患者血漿中SOD活性的降低。 （1996），Chiou和Hu（1999），Manoharan等。（2004年）。 SOD活性的降低可能是由於增加的脂質氫過氧化物所證明的ROS的內源性產生增加。 為了支持這一觀察結果，發現血漿LOOH與檢查患者中的SOD活性呈負相關。

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Compared with controls, significant elevation of CAT activity was recorded only in patients with hyperplasia complex while mild elevation was observed in the other groups. However, GPx activity was significantly increased only in patients with polypus endometrii. Other groups had lowered GPx activity, which was significant for the subjects diagnosed with either form of hyperplasia or adenocarcinoma. The observed changes also point to different antioxidant defense properties in various gynecological pathologies. Previous studies have reported elevated CAT and GPx activities in cervicitis patients (Chiou and Hu, 1999; Manoharan et al., 2004) and lowered activities of these enzymes in myoma patients (Chiou and Hu, 1999). In cancer patients, both lowered (Chiou and Hu 1999; Manoharan et al., 2004) and increased (Mila-Kierzenkowska et al., 2004) CAT activity in blood was observed.

Catalase is considered to play a greater role in protecting erythrocytes against oxidative stress than GPx (Gaetani et al., 1996; Mueller et al., 1997) although their significance in H202 decomposition is still not clear (Nagababu et al., 2003). Also it is well known that reactive oxygen metabolites such as hydrogen peroxide and superoxide anion increase in various pathological conditions and superoxide anion radical inactivates CAT (Kono and Fridovich, 1982) and GPx (Blum and Fridovich, 1985). Decreased SOD activity, observed in this study, would be expected to further elevate superoxide anion levels. It was also proposed that superoxide anion channel allows the transport of superoxide and other free radicals into the red cell, where they are deactivated by the erythrocyte antioxidant system (Richards et al., 1998). According to our results, in blood of examined gynecological patients, CAT activity seems to be unimpaired and GPx enzyme seems to be more sensitive to elevated levels of superoxide. In addition, lipid hydroperoxides were found to be positively correlated with CAT and negatively correlated with GPx activities in the examined patients.

Besides, decreased GPx activity, recorded in all groups except in polypus patients, might also be due to depletion of glutathione. Namely, oxidative stress was shown to induce the efflux of oxidized glutathione, consequently decreasing its content in erythrocytes and leading to their shorter life (Prchal et al., 1975; Thorn et al., 1997; Sharma et al., 2000). Similar observation was made by Manoharan et al. (2004) for cervical cancer patients and it was further supported with the finding of lowered glucose 6-phosphate dehydrogenase activity and NADPH production. Remarkably reduced glutathione reducíase activity recorded in our study is in accordance with these observations. Also, reduction of erythrocyte GPx and GR activities besides GSH depletion is considered responsible for increased heme degradation as shown by Nagababu et al. (2003). Similar findings on GPx and GR activities in our study could also point to further deterioration of oxidative stress conditions based on heme degradation in gynecological patients.

In summary, this study shows that patients with polypus or myoma, or either form of hyperplasia or adenocarcinoma have enhanced lipid peroxidation and LOOH/GPx ratio, as well as altered activities of antioxidant enzymes in peripheral blood circulation. Although alterations vary with the enzyme type and diagnosis, both reduction in antioxidants and elevation of lipid peroxidation were observed in general. The lowered activity of antioxidant enzymes in gynecological patients could be a result of disturbed redox status, while elevated lipid peroxidation seems to be a consequence of the disease rather than its cause. Furthermore, the LOOH/GPx ratio, which increases with the severity of the disease, suggests a greater oxidative stress status that can be related to the different uterine pathology. Such ratio could also be taken as an indicative parameter of oxidative stress in blood of gynecological patients.

It is known that in response to acute oxidative stress antioxidants may be consumed to prevent oxidative damage, and then may be supplied through the antioxidant network. However, in the cases of the observed gynecological pathologies it seems that prolonged oxidative stress elevates free radical production and induces consumption of antioxidants, which in turn further aggravate the free radical damage and increase the chance of developing uterine cancer. Indeed, the results obtained in this study show that observed changes of AO status, LOOH level, and LOOH/GPx ratio in peripheral circulation of gynecological patients are more pronounced in premalignant (hyperplastic) and malignant (ACE) lesions, compared with benign uterine changes (polypus and myoma). Further investigation should determine whether lipid hydroperoxides level and AOE activities in blood of such patients might be used as additional parameter in clinical evaluation of gynecological disorders.

ACKNOWLEDGEMENT

The work was financially supported by the Ministry of Science and Environmental Protection of the Republic of Serbia (塞爾維亞) (Grant 143035).

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Corresponding author: Dr. Snezana B. Pajovic, Principal scientist, Laboratory for Molecular Biology and Endocrinology, Vinca Institute for Nuclear Sciences, P. O. Box 522, 11001 Belgrade, Serbia (塞爾維亞), Tel +381 (11) 2455 561, Fax +381 (11) 2455 561, E-mail: pajovic@vin.bg.ac.yu

Received: April 13, 2006. Accepted: August 29, 2006
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