Expression of selenium-independent glutathione peroxidase 5 (GPx5) in the epididymis of Small Tail Han sheep

Li, Ruilan,Fan, Xiaomei,Zhang, Tong,Song, Huizi,Bian, Xiaona,Nai, Rile,Li, Jinquan,Zhang, Jiaxin Asian Australasian Association of Animal Productio 2018 Animal Bioscience Vol.31 No.10

Objective: Selenium-independent glutathione peroxidase (GPx5) is specifically expressed in the mammalian epididymis and plays an important role in protecting sperm from reactive oxygen species and lipid peroxidation damage. This study investigates GPx5 expression in the epididymis of Small Tail Han sheep. Methods: GPx5 expression was studied in three age groups: lamb (2 to 3 months), young (8 to 10 months), and adult (18 to 24 months). The epididymis of each age group divided into caput, corpus and cauda, respectively. Analysis the expression quantity of GPx5 in epididymis and testis by real-time fluorescent quantitative polymerase chain reaction and Western blot. Finally, GPx5 protein locating in the epididymis by immunohistochemical. Results: The results demonstrate that in the lamb group, the GPx5 mRNA, but not protein, can be detected. GPx5 mRNA and expressed protein were detected in both the young and adult groups. Moreover, both the mRNA and protein levels of GPx5 were significantly higher in the young group than in other two groups. When the different segments of epididymis were investigated, GPx5 mRNA was expressed in each segment of epididymis regardless of age. Additionally, the mRNA level in the caput was significantly higher than that in corpus and cauda within same age group. The GPx5 protein was in the epithelial cells' cytoplasm. However, GPx5 mRNA and protein were not detected in the testis. Conclusion: These results suggest that GPx5 is mainly expressed in the epididymis of Small Tail Han sheep, and that the expression level of GPx5 is associated with age. Additionally, GPx5 was primarily expressed in the epithelial cells of the caput. Taken together, these studies indicate that GPx5 is expressed in the epididymis in all age grades.

Expression Profile of Glutathione Peroxidase Genes in the Male Reproductive System of Mice Exposed to Ginseng Extracts

Mi-Ra Kim,Jung-Min Yon,Se-Ra Lee,In-Jeoung Baek,Yun-Bae Kim,Beom-Jun Lee,Young Won Yun,Sang-Yoon Nam 한국실험동물학회 2008 Laboratory Animal Research Vol.24 No.2

Ginseng is one of the most common herbal medicines in the Orient which has been used for the treatment of disease due to its wide spectrum of medicinal effects, such as tonic, immunomodulatory, antioxidant, and anti-aging activities. However, there are only a few reports on the effects of Korean ginseng on the reproductive organs in animals and humans. To understand the antioxidative effect of Korean ginseng on the male reproductive system, we analyzed the mRNA expression patterns of glutathione peroxidase (GPx) family [cytosolic (GPx1), gastrointestinal (GPx2), and phospholipid hydroperoxide (GPx4) types] in the testes, epididymes, prostates, and seminal vesicles of mice exposed to Korean ginseng. Korean ginseng extracts (20, 200, and 2,000 mg/kg body weight) were treated to 7-weekold male mice for 9 weeks daily per oral. Total RNAs were extracted from testis, epididymis, prostates, and seminal vesicles, and then RT-PCR was performed with the specific primers of each GPx genes. In testis, all type of GPx mRNA expression was similar to that of control group. However, the gene expression of GPx2 was decreased in the epididymis exposed to 2,000 ㎎/㎏ of Korean ginseng, but it was no significant difference. The gene expression of GPx1 in prostates was tend to decrease slightly compare to control group, but those of GPx2 and GPx4 were weakly increased by Korean ginseng treatments. On the contrary, the gene expressions of GPx2 and GPx4 in seminal vesicles were decreased slightly compare to control group. These findings suggest that Korean ginseng may influence the antioxidant system of male reproductive organs in a differential manner.

Genetic overexpression of glutathione peroxidase-1 attenuates microcystin-leucine-arginine-induced memory impairment in mice

Shin, Eun-Joo,Hwang, Yeong Gwang,Pham, Duc Toan,Lee, Ji Won,Lee, Yu Jeung,Pyo, Dongjin,Lei, Xin Gen,Jeong, Ji Hoon,Kim, Hyoung-Chun Elsevier 2018 Neurochemistry International Vol.118 No.-

<P><B>Abstract</B></P> <P>Microcystin-leucine-arginine (MCLR) is the most common form of microcystins, which are environmental toxins produced by cyanobacteria, and its hepatotoxicity has been well-documented. However, the neurotoxic potential of MCLR remains to be further elucidated. In the present study, we investigated whether intracerebroventricular (i.c.v.) infusion of MCLR induces mortality and neuronal loss in the hippocampus of mice. Because we found that MCLR impairs memory function in the hippocampus at a low dose (4 ng/μl/mouse, i.c.v.) without a significant neuronal loss, we focused on this dose for further analyses. Results showed that MCLR (4 ng/μl/mouse, i.c.v.) significantly increased oxidative stress (i.e., malondialdehyde, protein carbonyl, and synaptosomal ROS) in the hippocampus. In addition, MCLR significantly increased superoxide dismutase (SOD) activity without corresponding induction of glutathione peroxidase (GPx) activity, and thus led to significant decrease in the ratio of GPx/SODs activity. The GSH/GSSG ratio was also significantly reduced after MCLR treatment. GPx-1 overexpressing transgenic mice (GPx-1 Tg) were significantly protected from MCLR-induced memory impairment and oxidative stress. The DNA binding activity of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) in these mice was significantly enhanced, and the ratios of GPx/SODs activity and GSH/GSSG returned to near control levels in the hippocampus. Importantly, memory function exhibited a significant positive correlation with the ratios of GPx/SODs activity and GSH/GSSG in the hippocampus of MCLR-treated non-transgenic (non-Tg)- and GPx-1 Tg-mice. Combined, our results suggest that MCLR induces oxidative stress and memory impairment without significant neuronal loss, and that GPx-1 gene constitutes an important protectant against MCLR-induced memory impairment and oxidative stress via maintaining antioxidant defense system homeostasis, possibly through the induction of Nrf2 transcription factor.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A low dose of MCLR induces memory losses without significant neuronal degeneration. </LI> <LI> MCLR-induced memory loss is possibly via reductions in GPx/SODs and GSH/GSSG. </LI> <LI> GPx-1 overexpression inhibits MCLR-induced memory loss via up-regulation of Nrf2. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

GPX1 및 hOGG1 유전자다형성에 따른 유전자의 산화적 손상 및 폐암 발생 위험도 평가

이철호,이계영,최강현,홍윤철,노성일,엄상용,고영준,장연위,임동혁,강종원,김헌,김용대,Lee, Chul-Ho,Lee, Kye-Young,Choe, Kang-Hyeon,Hong, Yun-Chul,Noh, Sung-Il,Eom, Sang-Yong,Ko, Young-Jun,Zhang, Yan-Wei,Yim, Dong-Hyuk,Kang, Jong-Won,Kim, H 대한예방의학회 2006 예방의학회지 Vol.39 No.2

Objectives : Oxidative DNA damage is a known risk factor of lung cancer. The glutathione peroxidase (GPX) antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides plays a significant role in protecting cells from the oxidative stress induced by reactive oxygen species. The aim of this case-control study was to investigate effects of oxidative stress and genetic polymorphisms of the GPX1 genes and the interaction between them in the carcinogenesis of lung cancer. Methods : Two hundreds patients with lung cancer and 200 age- and sex-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and their environmental exposure to PAHs. The genotypes of the GPX1 and 8-oxoguanine glycosylase 1 (hOGG1) genes were examined and the concentrations of urinary hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) were measured. Results : Cigarette smoking was a significant risk factor for lung cancer. The levels of urinary 8-OH-dG were higher in the patients (p<0.001), whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. The GPX1 codon 198 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Pro/Leu or Leu/Leu genotype of GPX1 were at a higher risk for lung cancer (adjusted OR=2.29). In addition, these individuals were shown to have high urinary 8-OH-dG concentrations compared to the individuals with the GPX1 Pro/Pro genotype. On the other hand, the polymorphism of the hOGG1 gene did not affect the lung cancer risk and the oxidative DNA damage. Conclusions : These results lead to a conclusion that individuals with the GPX1 Pro/Leu or Leu/Leu genotype would be more susceptible to the lung cancer induced by oxidative stress than those individuals with the Pro/Pro genotype.

Effects of Licorice (Glycyrrhiza glabra) on the Gene Expression of Glutathione Peroxidase in the Female Reproductive System of Rats

Se-Ra Lee,Jung-Min Yon,Mi-Ra Kim,Yan-Jin,In-Jeoung Baek,Yun-Bae Kim,Byeongwoo Ahn,Beom-Jun Lee,Sang-Yoon Nam,Young Won Yun 한국실험동물학회 2007 Laboratory Animal Research Vol.23 No.1

To understand the antioxidative effect of licorice on the female reproductive system, we analyzed the mRNA expression patterns of glutathione peroxidase (GPx) family (type 1-4) in the ovary and uterus of rats exposed to licorice. Licorice, the root of the leguminous Glycyrrhiza, is one of the most frequently employed botanicals in foods and traditional medicines, which is known to have antioxidant, anti-tumor, anti-allergic and antiviral activities, in addition to estrogenic properties. However, there is no report on the effects of licorice in the reproductive organs. Licorice extracts (0, 0.5, 1, and 2 g/㎏ body weight) were treated to 8-week-old female rats for 4 weeks daily per oral. Total RNAs were extracted from ovary and uterus and then RT-PCR analysis was performed with the specific primers of each GPx enzyme. In ovaries, GPx1, GPx3, and GPx4 mRNA levels were slightly decreased compared with those of control group. Especially, GPx3 mRNA expression was decreased dose-dependantly in ovaries. However, GPx2 mRNA was weakly increased in ovary. On the contrary, the gene expression of GPx1-3 in uteri tended to increase slightly compared to control group. GPx4 mRNA expression was decreased by 0.5 g/㎏ of licorice in uterus, but increased by treatment with 1 and 2 g/㎏ of licorice. These findings indicate that licorice maybe differently influenced on the antioxidant systems of ovary and uterus.

지구력 훈련기간 중의 간헐적 저산소 환경노출이 산화스트레스에 미치는 영향

정동식 ( Dong Sik Joung ),이종각 ( Jong Kak Lee ),김영수 ( Young Soo Kim ),박동호 ( Dong Ho Park ),성봉주 ( Bong Joo Sung ),조남홍 ( Nam Hong Cho ),오인석 ( In Seok Oh ) 한국스포츠정책과학원(구 한국스포츠개발원) 2004 체육과학연구 Vol.15 No.3

본 연구는 저지대에서 지구력 훈련을 수행하면서 수면시간에만 저산소 환경에 노출시키는 방법을 이용하여 고지대 체류-저지대 훈련이라는 새로운 개념의 훈련 방법이 산화 스트레스와 항산화 효소에 미치는 영향을 규명하는데 그 목적이 있었다. 연구 대상은 고등학교 육상 장거리 선수 20명으로 선정하였으며, 이들을 임의로 실험집단 10명과 비교집단 10명으로 구분하였다. 실험집단은 4주 동안 3,000m 고도에 해당하는 저산소 텐트에서 하루 8시간씩 휴식 및 수면을 취하고 지구력 훈련은 저강도 장거리달리기와 고강도 인터벌 훈련을 병행하였으며 비교집단은 저산소 노출을 제외한 일체의 생활을 실험집단과 동일하게 통제하였다. 처치전 최대운동 전후와 4주간 처치후의 최대운동 전후에 산화 스트레스 및 항산화 효소 변인으로 MDA(malondialdehide) 수준, SOD(superoxide dismutase) 및 GPX(glutathione peroxidase) 활성을 측정하여 다음과 같은 결과를 얻었다. ① MDA 수준은 실험집단의 경우 처치전에는 최대운동으로 인해 증가하였으며(p<.05), 4주간처치 후에도 안정시 및 운동 후에 증가 경향을 보였으나, 처치전 최대운동 후에만 비교집단보다 유의하게 높았다(p<.05). ② SOD 활성은 실험집단의 경우 처치전에는 최대운동으로 인해 유의하게 감소(p<.05)하였고, 4주간의 처치 후에는 안정시에 처치전보다 현저한 증가(p<.05)상태를 보이고 최대운동 후에 약간 감소하는 경향을 보였으며, 처치4주 후의 안정시 및 최대운동 후에 비교집단보다 낮은 경향을 나타냈으나 최대운동 후에만 유의하게 낮은 것으로 나타났다(p<.05). ③ GPX 활성은 실험집단의 경우 처치 전에 최대운동으로 거의 변화를 나타내지 않았고 처치4주의 안정시 및 최대운동 후에는 처치전보다 현저히 증가된 상태를 보였으나(p<.05), 비교집단과 유의한 차이를 보이지는 않았다. 이상의 결과에 의하면 일시적인 최대운동은 산화 스트레스를 증가시키며 여기에 대항하는 적혈구의 SOD와 GPX의 활성을 약간 감소시키거나 변화시키지 않는 반면, 4주간의 고강도 지구력 훈련은 산화 스트레스의 증가와 이에 대응하는 SOD 및 GPX 활성의 증가를 유발하는 효과를 나타낸다고 결론 내릴 수 있다. 또한, 지구력 훈련과 병행한 3000m 고도의 저산소 노출은 산화 스트레스와 항산화 효소의 활성을 추가로 증가시키지는 않는다. The purpose of the present investigation was to determine the effects of "living high, training low" during a period of regular training on the oxidative stress and anti-oxidative enzymes. Ten long distance runners of B high school slept for 8-hour per day for 4-week at a simulated altitude of 3,000m in normobaric hypoxia (HIGH), while ten team-mates slept at the normoxia (CONDITION). HIGH and CONDITION subjects equally trained as a group throughout the 4-week study. Both baseline level(D1) and immediately after incremental exercise(DT1) test of malondialdehide(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GPX) were measured 1 day prior to sleeping in hypoxia. These measures were repeated after 4-week of simulated altitude exposure before the incremental test(D2) and immediately after the test(DT2). The results were as following; ① The levels of MDA in both groups increased significantly(p<.05) after the incremental test(DT1 & DT2) in comparison to the D1 and D2, respectively. MDA levels tended to be increased above the pre-hypoxia level over 4-week of hypoxia. However, MDA level in HIGH significantly increased (p<.05) after DT1 compared to the level in CONTROL. ② The activity of SOD in both groups decreased significantly(p<.05) after the incremental test(DT1) compared to the D1. Thereafter, SOD activity tended to be increased (p<.05) above the pre-hypoxia level over 4-week of the study. However, SOD activity in HIGH significantly decreased (p<.05) after DT2 compared to MDA level in CONTROL. ③ there was no significant increase in GPX activity of both groups immediately after the test(DT1 vs D1) while GPX activity in both groups at D2 significantly decreased (p<.05) after DT2. without group difference. We concluded that acute maximal exercise might increase in oxidative stress with either increase or non-change in SOD and GPX activities. However, vigorous endurance training during 4-week might increase in oxidative stress with increase in both SOD and GPX activities. In addition, sleeping in moderate hypoxia(3,000m) with vigorous endurance training couldn`t additionally increase in both oxidative stress and anti-oxidants but appropriate method for reducing oxidative stress should be provided.

Glutathione peroxidase‐1 overexpressing transgenic mice are protected from neurotoxicity induced by microcystin‐leucine‐arginine

Shin, Eun‐,Joo,Hwang, Yeong Gwang,Pham, Duc Toan,Lee, Ji Won,Lee, Yu Jeung,Pyo, Dongjin,Jeong, Ji Hoon,Lei, Xin Gen,Kim, Hyoung‐,Chun John Wiley Sons, Inc. 2018 Environmental toxicology Vol.33 No.10

<P><B>Abstract</B></P><P>Although it has been well‐recognized that microcystin‐leucine‐arginine (MCLR), the most common form of microcystins, induces neurotoxicity, little is currently known about the underlying mechanism for this neurotoxicity. Here, we found that MCLR (10 ng/μL/mouse, i.c.v.) induces significant neuronal loss in the hippocampus of mice. MCLR‐induced neurotoxicity was accompanied by oxidative stress, as shown by a significant increase in the level of 4‐hydroxynonenal, protein carbonyl, and reactive oxygen species (ROS). Superoxide dismutase‐1 (SOD‐1) activity was significantly increased, but glutathione peroxidase (GPx) level was significantly decreased following MCLR insult. In addition, MCLR significantly inhibited GSH/GSSG ratio, and significantly induced NFκB DNA binding activity. Because reduced activity of GPx appeared to be critical for the imbalance between activities of SODs and GPx, we utilized GPx‐1 overexpressing transgenic mice to ascertain the role of GPx‐1 in this neurotoxicity. Genetic overexpression of GPx‐1 or NFκB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly attenuated MCLR‐induced hippocampal neuronal loss in mice. However, PDTC did not exert any additive effect on neuroprotection mediated by GPx‐1 overexpression, indicating that NFκB is a neurotoxic target of MCLR. Combined, these results suggest that MCLR‐induced neurotoxicity requires oxidative stress associated with failure in compensatory induction of GPx, possibly through activation of the transcription factor NFκB.</P>

GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress

Hyeon Ju Kim,Yoseob Lee,Sungsoon Fang,김원,김효정,김재우 생화학분자생물학회 2020 BMB Reports Vol.53 No.6

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASHfibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor- (TGF-) and free fatty acids (FFA)- treated LX-2 cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis. Consistently, GPx7 overexpression in LX-2 cells led to the suppression of ROS production and reduced the expression of pro-fibrotic and pro-inflammatory genes. Further, NASH fibrosis induced by choline-deficient amino acid defined, high fat diet (CDAHFD) feeding was significantly accelerated by knockdown of GPx7, as evidenced by up-regulated liver fibrosis and inflammation compared with CDAHFD control mice. Collectively, these results suggest that GPx7 might be a novel therapeutic target to prevent the progression and development of NAFLD.

The GPX1 Pro198Leu polymorphism in gastric cancer patients with and without Helicobacter pylori infection

Mohammad‑Taher Moradi,Kheirollah Yari,Zohreh Rahimi 한국유전학회 2017 Genes & Genomics Vol.39 No.11

Helicobacter pylori infection could induce oxidative stress. Oxidative stress is involved in the pathogenesis of gastric diseases. Glutathione peroxidase 1 (GPX1), is part of the enzymatic antioxidant defense, preventing oxidative damage. The aim of the present study was to assess the association of GPX1 Pro198Leu genotypes with gastric cancer in patients with and without H. pylori infection in a population of Northern Iran. The present case-control study consisted of 50 patients with gastric cancer and 78 cancer-free subjects as controls. Extraction of DNA was performed on bioptic samples and the GPX1 genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of GPX1 Pro/Pro, Pro/Leu and Leu/Leu genotypes in controls were 21.8, 71.8 and 6.4%, respectively. However, in gastric cancer patients, the frequencies of 34, 56 and 10% were observed for Pro/Pro, Pro/Leu and Leu/Leu genotypes, respectively (p = 0.185). In 38 (76%) patients infected with H. pylori, the frequencies of Pro and Leu alleles were 94.7 and 3.3%, respectively. There was a higher frequency of combined genotype of Pro/Leu + Leu/ Leu (94.7%) in H. pylori positive patients than that in patients without H. pylori infection (75%, p = 0.047). The presence of this genotype tended to increase the risk of H. pylori related gastric cancer by 5.88–fold (p = 0.069) in our population. Our findings indicated the absence of association between the GPX1 Pro198Leu polymorphism and the risk of gastric cancer in an Iranian population. However, we detected an association between H. pylori related gastric cancer with GPX1 Pro/Leu + Leu/Leu genotype.

단기간 비타민 투여가 발레 동작수행시 MDA 및 SOD, GPx 활성도에 미치는 영향

김민희,홍성욱 한국무용과학회 2012 한국무용과학회지 Vol.26 No.-

This study of ballet performance when performing short-term intake of antioxidants lipid peroxidation indicator MDA and SOD, GPx examined the impact of the activity. This study will be carried out among eight female ballet dancers in seven days in which these women who are being studied will be under the consumption of antioxidants that will be closely monitored. George Ballanchine’s ballet nutcracker waltz of the flowers was carried for a total of 12 minutes and 52 seconds. Through the exercise intensity of the work of the polar heart rate when measured, the blood samples for the analysis of antioxidants before-take were performed at rest immediately after work during the 7 days of antioxidants after take when the performance was stable immediately after work with each 7ml blood. MDA blood concentrations of antioxidants before take and after take showed significantly lower SOD and GPx activity, but there was no significant difference. At least in summary, the results when performing ballet to promote oxidative stress antioxidant intake appeared to be generated when performing the operation which was found to inhibit lipid peroxidation. 본 연구는 단기간 비타민 섭취가 발레작품 수행 시 지질과산화 지표인 MDA와 SOD, GPx의 활성도에 미치는 영향을 살펴보았다. 8명의 여성 발레무용수를 대상으로 비타민 C, E를 7일간 섭취시켰다. 발레작품은 조지발란신의 호두까기 인형중 꽃의 왈츠를 수행하였으며 총 12분 52초로 구성되었다. 작품의 운동강도는 polar를 통해 심박수를 측정하였으며, 혈액채취의 분석은 비타민 C, E 섭취 전 안정 시 와 작품수행직후 그리고 7일간 비타민 섭취 후 안정 시, 작품수행직후 각각 7ml의 혈액을 채혈하였다. 혈중 MDA 농도는 비타민 섭취전 보다 섭취 후 유의하게 낮게 나타났으나 SOD와 GPx 활성도는 유의한 차이가 없는 것으로 나타났다. 이상 결과를 종합해보면 발레작품 수행 시 산화스트레스가 촉진되는 것으로 나타났고 항산화제 섭취는 동작수행시 생성되는 지질과산화를 억제시키는 것으로 확인되었다. 따라서 항산화제인 비타민 복용은 고강도의 훈련과정에서 나타나는 산화스트레스에 대해 생체내의 방어기전인 항산화효소의 활성을 증가시키고 지질과산물의 생성을 감소시켜 산화적 스트레스에 대한 저항력을 증가시켜 줄 수 있을 것으로 생각되어 무용수들의 체계적인 건강관리 시스템의 도움에 긍정적인 형향을 미칠 것으로 사료된다.