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Selenium and the Thioredoxin and Glutaredoxin Systems

Biomedical and Environmental Sciences 1997年第2期10卷 271-279页

作者： MIKAEL BJORNSTEDT SUSHIL KUMAR LINDA BJ■RKHEM GIANNIS SPYROU AND ARNE HOLMGREN(The Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden Department of Bioscience, KAROLINSKA INST NOVUM DEPT BIOSCI S-14157 HUDDINGE SWEDEN

Thioredoxin (Trx) is a small ubiquitous dithiol protein which together with the FADcontaining enzyme thioredoxin reductase (TR) and NADPH (the Trx system) is a hydrogen donor for ribonucleotide reductase essential for DNA synthesis and a general protein disulfide reductase involved in redox regulation. Selenite, selenodiglutathione (GS-Se-SG) and selenocystine are efficiently reduced by thioredoxins and also directly by NADPH and mammalian TR but not by the E. coli enzyme. Incubation of selenite or GS-Se-SG with the Trx system or with mammalian TR results in a rapid formation of selenide, which by redox cycling with oxygen may cause a large non-stoichiometric oxidation of NADPH. Selenocystine is efficiently reduced into two molecules of the selenol amino acid selenocysteine by mammalian TR with a Km-value (6μmol·L-1 ) and a high turnover number (kcat, 3200 min-1) almost identical to the natural substrate Trx-S2. TR also directly reduces lipid hydroperoxides and this peroxidase reaction is strongly stimulated by the presence of catalytic amounts of free selenocysteine. Glutaredoxin (Grx) which catalyzes GSH dependent disulfide reduction also via a redox-active disulfide and Trx are both efficient electron donors to the hut-nan plasrna glutathione peroxidase providing a mechanism by which human plasma glutathione peroxidase may reduce hydroperoxides in an environment almost free from glutathione. Selenate is reduced by Grx and Trx in the presence of GSH. The DNA-binding of the transcription factor AP-1 is strongly inhibited by GS-Se-SG and selenite. Furtherrnore, selenide formed by TR-mediated reduction of selenite and GS-Se-SG inhibits lipoxygenase and changes the electron spin resonance spectrum of the active site iron. Mammalian TR with two subunits of 57 kDa has recently been cloned and shown to be homologous to glutathione reductase. The rat enzyme contains a selenocysteine residue in a unique Cterminal position and a conserved SEClS sequence directing insertion

关键词： NADPH Selenium and the Thioredoxin and Glutaredoxin Systems GSH USA ADF

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Recent advances in estrogen-signaling and new sites for pharmacological interventions

Recent advances in estrogen-signaling and new sites for phar...

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第十五届国际药理学大会

作者： Jan-Ake Gustafsson Department of Biosciences and Nutrition novum Karolinska Institutet Stockholm

＜正＞ Both in vitro and in vivo. ERβ acts as an antiproliferative principle in several tissues, e g the prostate where ERβ is antiproliferative. proapoptotic and prodifferentiative. An ERβ agonist developed by Eli Lilly shows all of the anticipated biological effects on the prostate, namely reduced cellular proliferation and increased apoptosis, leading to a diminished size of both mouse and rat prostate. This opens up hitherto unthought-of pharmaceutical possibilities in treating prostate disorders in humans, including both benign prostatic hyperplasia and prostate carcinoma. It now appears quite clear that ERβ also exerts an antiproliferative effect on human breast cancer cells both in vitro and in vivo;there seems to be sufficient indications for a pharmaceutical potential of ERβ agonists in treatment of breast cancer. A similar case can be made for use of ERβ agonists in treatment of colon cancer. Furthermore. ERβ is of major importance in estrogenic regulation of the immune system. Wyeth-Ayerst has reported extremely encouraging results of ERβ agonists in treatment of rodent models of inflammatory bowel disease （IBD）. rheumatoid arthritis and endometriosis.

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Estrogen receptorβexpression in the embryonic brain regulates development of calretinin-immunoreactive GABAergic interneurons

Estrogen receptorβexpression in the embryonic brain regulat...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Margaret WARNER Jan-Ake GUSTAFSSON Division of Medical Nutrition Department of Biosciences and NutritionKarolinska InstitutetNovum S14186Sweden

Our previous studies with ERβ mice demonstrated that ERβis necessary for embryonic development of the brain as early as E14.5 and is involved in neuronal *** early effects of estrogen receptors were unexpected because estradiol synthesis and action in the brain are well documented to occur at *** the presence of ERβin the embryonic brain was not demonstrated it remained possible that the developmental abnormalities in ERβ mice were due to indirect effects of estrogen action on the *** the present study we examined the distribution of ERβin the developing brain and identified a population of ERP-regulated ***βappears in the brain at *** localized in the wall of midbrain,neuromere,hypothalamus,thalamus and basal plate of *** E15.5 and E16.5,ERβexpression increased in the hypothalamus,thalamus and midbrain and appeared in the limbic *** E18.5,ERβexpression was strongly and widely expressed throughout the brain including cerebellum and striatum,while there were very few positive cells in the ventricular *** the paraventricular thalamic nucleus and parafascicular nucleus,most of the calretinin-immunopositive interneurons expressed ERβ.In ERβ mice,calretinin expression was markedly lower than in WT mice in the hippocampus,thalamus and amygdala both at E16.5 and at *** growth factor receptor expression was lower in the cortex of ERβ than WT mice at E15.5,and unlike WT mice,was absent from the superficial marginal *** findings suggest that ERp in the embryonic brain is necessary for the development of calretininimmunoreactive GABAergic intemeurons and for neuronal migration in the cortex through modulating EGFR expression at middle and later embryonic stages.

关键词： Brain ERβ interneuron calretinin development

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UV Photoproduct Levels in Melanocytic Nevi and Surrounding Epidermis in Human Skin in situ

UV Photoproduct Levels in Melanocytic Nevi and Surrounding E...

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Asian-Pacific Conference of Tumor Biology 2001

作者： ChunyanZhao KariHemminki ErnaSnellman ChristerT.Jansen Department of Biosciences at novum Karolinska Institute 14157 Huddinge Sweden Department of Biosciences at novum Karolinska Institute 14157 Huddinge Sweden Department of Dermatology Paijat-Hame Central HospitalFIN 15850 LahtiFinland Department of Dermatology University of Turku20520 TurkuFinland

＜正＞Melanocytic nevi are localized benign proliferations of *** development of nevi and cuta-neous malignant melanoma（CMM）has been linked to sun *** risk factors for CMM includesun exposure,pigmentary traits,and a family history of *** damage induced by ultravioletradiation（UVR）is considered to have a direct role in the initiation of skin *** mein products in-duced by UV are dipyrimidine lesions:cyclobutane pyrimidine dimers（CPD）and 6-4 pyrimidine-pyrimidone *** study compares the induction of photoproducts in nevi and in surrounding

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Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation

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Frontiers of Medicine 2008年第3期2卷 235-238页

作者： Rong LIU Ji ZENG Xinwen ZHOU Jinjing PEI Jianzhi WANG Department of Pathophysiology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Karolinska Institutet KI-Alzheimer Disease Research Center(KI-ADRC)NovumHuddingeSweden Clinical Laboratory of Union Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau *** Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein,and the phosphorylation levels of PP2A Y307 and tau at different sites,as well as PP2A activity were detected at different time points after siRNA *** hours after siRNA transfec-tion,the protein level of Src was dramatically decreased,with decreased PP2A Y307 ***,the total PP2A protein level was also decreased,together with a decreased PP2A *** was hyperpho-sphorylated at the Ser198/199/202 *** factors may be involved in the cellular regulation of PP2A *** Src expression could induce inactivation of PP2A and tau hyperphosphorylation.

关键词： Src kinase protein phosphatase 2A tau pro-tein Alzheimer’s disease

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MD simulation of high-resolution X-ray structures reveals post-translational modification dependent conformational changes in HSF-DNA interaction

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Protein & Cell 2016年第12期7卷 916-920页

作者： Han Feng Sheng Wang Ling Guo Avinash S. Punekar Rudolf Ladenstein Da-Cheng Wang Wei Liu National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Key Laboratory of Molecular Biophysics of the Ministry of Educa- tion College of Life Science and Technology Huazhong University of Science and Technology Wuhan 430074 China Institute of Immunology The Third Military Medical University Chongqing 400038 China Department of Biosciences and Nutrition Karolinska Institutet NOVUM 14183 Huddinge Sweden

Dear Editor, Heat shock factors （HSFs） constitute a transcription factor family playing regulatory roles in maintaining cellular protein homeostasis or mediating cell differentiation and develop- ment （Akerfelt et al., 2010, Bjork and Sistonen 2010, Westerheide et al., 2012）. Some human diseases such as cancer and neurodegeneration are often linked with mal- function of HSFs （Dai et al., 2007, Neef et al., 2011, Scherz- Shouval et al., 2014）. The human HSF family consists four members： HSF1-4, which exhibit tissue-specific expression profiles and possess unique but overlapping functions. HSF1 is the major regulator of the heat shock response.

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Spouses Who Donate Seem to Be the Winners – A Questionnaire Study of Kidney Donors Long-Term

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Open Journal of Nephrology 2012年第3期2卷 44-48页

作者： Annette Lennerling Abdul Rashid Qureshi Ingela Fehrman-Ekholm Baxter novum CLINTEC Karolinska Institute Stockholm Sweden Renal Department Karolinska University Hospital Stockholm Sweden Transplant Institute Sahlgrenska University Hospital Gothenburg Sweden

Background:Living donor kidney transplantations have been performed at Sahlgrenska University Hospital in Gothenburg, Sweden since 1965. In this study we wanted to explore the living kidney donor’s long-term experiences of the donation. Methods: Of 1110 consecutive living donors throughout 1965-2005, 823 were available for our questionnaire study. Results:Totally 692 replied to the questionnaire, 65% were females. The most common relation to the recipients was siblings (284), parents (262) and spouses (96). Time since donation was median 15 years (2 - 43). The initiative to donate came from the donors themselves in 69%. The dominating motives for donation were a wish to help, worries about the recipient not receiving a transplant and the knowledge that one could live a normal life with one kidney. The majority of the donors, felt well informed about potential risks both short-term and long-term. Depression post donation was reported by few donors, 2.3% and persisting pain by 4.3%. Comparisons between sibling donors and spouse donors show a significant difference (p Conclusions:Our study shows that the donor population is in good psychosocial health. It is a positive progress that spouses can be living kidney donors - they seem to be the winners.

关键词： Living Kidney Donors Long-Term Follow-Up Motives Sibling Spouse Questionnaire

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Skin Cancer Detection Using Temperature Variation Analysis

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Engineering（科研） 2013年第10期5卷 18-21页

作者： Ahmed M. Nasr Moustafa Hamed Hamid Muhammed Moustapha Hassan Clinical Research Center novum Karolinska University Hospital Huddinge Stockholm Sweden Division of Informatics Logistics and Management School of Technology and Health STH Royal Institute of Technology KTH Stockholm Sweden

In the medical field, new technologies are incorporated for the sole purpose of enhancing the quality of life for the patients and even for the normal healthy people. Infrared technology is one of the technologies that have some applications in both the medical and biological fields. In this work, the thermal infrared (IR) measurement is used to investigate the potential of skin cancer detection. IR enjoys non-invasive and non-contact advantages as well as favorable cost, apparently. It is also very well developed regarding the technological and methodological aspects. IR per se is an electro-metric radiation that all objects emit when their temperature is above the absolute zero. And the human body is not different in this regard. The IR range extends, ideally, to cover wavelengths from 800 nanometer to few hundred micrometer. Cancer, in modern life, has grown tangibly due to many factors, such as life expectancies increase, personal habits and ultraviolet radiation exposures among others. Moreover, the significant enhancement of technologies has helped identifying more types of cancers than before. The sole purpose of this work is to investigate further IR technology methods and applications not yet matured in skin cancer detection to enhance the detection ability with higher safety level.

关键词： Infrared Skin Cancer Melanoma Thermal Detection

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迎接下一场石油危机的挑战

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国外社会科学文摘 1998年第1期 23-25页

作者：伊凡霍陈一铭陈威 novum国际能源勘查咨询公司董事长

在本世纪70年代的石油危机后,石油短缺现象消失了,石油价格也一直保持平稳状态。世界似乎不再为石油而焦虑了,但严峻的事实实际上依然存在着,那就是地球上的石油储量是有限的,而我们对它的消耗正以惊人的速度在增长着。70年代的危机只... 详细信息

在本世纪70年代的石油危机后,石油短缺现象消失了,石油价格也一直保持平稳状态。世界似乎不再为石油而焦虑了,但严峻的事实实际上依然存在着,那就是地球上的石油储量是有限的,而我们对它的消耗正以惊人的速度在增长着。70年代的危机只不过是油价的突然上涨,所以寻求别的石油供应来源就成了当务之急,同时各种鼓励节能的措施纷纷出台,使能源在供求关系上发生了转换,从而促使危机得以解决。但是,下一次在不远的将来隐隐呈现的石油危机比以往要严重得多。现在世界上几乎所有的有开采价值的大油田都已经被发现,一场新的永久性的

关键词：石油产量地球地质调查美国工业产品产量行星美利坚合众国北美洲油气杂志能源危机石油危机石油供应油气储量石油储量矿物燃料矿床油田欧佩克伊拉克-伊朗战争两伊战争非活性伊拉克

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俄罗斯西北部母乳喂养开始时间及持续时间的社会人口统计学决定因素

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世界核心医学期刊文摘（儿科学分册） 2005年第9期1卷 61-62页

作者： Grjibovski A.M. Yngve A. Bygren L.O. Sjstrm M. 贺莉 Unit for Preventive Nutrition Department of Biosciences at Novum Karolinska Institutet SE-141 57 Huddinge Sweden

Aim: This study examines socio-demographic determinants of initiation and duration of breastfeeding in a communitybased cohort in northwest Russia. Methods: All infants born to women who were registered at the antenatal clinics in Severodvinsk in 1999 comprised the cohort (n = 1399) and were followed up at 1 y. Data on maternal and infant characteristics as well as the duration of breastfeeding were obtained from medical records. Proportional hazard analysis was applied to quantify the effect of the selected factors on the risk of breastfeeding discontinuation adjusted for potential confounders. Results: Only 1.3% of infants were never breastfed. Breastfeeding rates were 75.0% and 47.2% at 3 and 6 mo, respectively. Maternal age and early initiation of prenatal care were positively associatedwith breastfeeding initiation rates. Increased risks of breastfeeding discontinuation were found in teenage mothers (OR = 1.45, 95% CI: 1.06-1.99), in mothers with basic education (OR = 1.68, 95% CI: 1.06-2.66) and in unmarried mothers (OR = 1.19, 95% CI: 1.03-1.38). Women with no previous deliveries were more likely to breastfeed longer (OR = 0.74, 95% CI: 0.62-0.90). Conclusions: Compared with previous studies in Russia, almost universal initiation and considerably higher rates of breastfeeding at specific time points were found. Social variations in initiation and duration of breastfeeding should raise concern of inequalities in breastfeeding practices in transitional Russia.

关键词：母乳喂养人口统计学持续时间妇女分娩医疗记录队列研究门诊登记混杂因素产前健康教育特异性

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