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2.
Hmi1p is a helicase in the yeast Saccharomyces cerevisiae required for maintenance of the wild-type mitochondrial genome. Disruption of the HMI1 ORF generates – and 0 cells. Here we demonstrate that, in – yeast strains, Hmi1p stimulates the synthesis of long concatemeric mitochondrial DNA molecules associated with a reduction in the number of nucleoids used for mitochondrial DNA packaging. Surprisingly, the ATPase negative mutants of Hmi1p can also stimulate the synthesis of long concatemeric – mitochondrial DNA molecules and support the maintenance of the wild-type mitochondrial genome, albeit with reduced efficiency. We show that, in the mutant hmi1–5 background, the wild-type mitochondrial DNA is fragmented; and we propose that, in hmi1 yeast cells, the loss of the wild-type mitochondrial genome is caused by this fragmentation of the mitochondrial DNA. 相似文献
3.
Katrin Trummal Külli T?nism?gi Ene Siigur Anu Aasp?llu Annika Lopp Tarvo Sillat Riste Saat Lagle Kasak Indrek Tammiste Priit Kogerman Nisse Kalkkinen Jüri Siigur 《Toxicon》2005,46(1):46-61
A novel endothelial cell apoptosis inducing metalloprotease (VLAIP) was found in the snake venom of Vipera lebetina. This metalloprotease is a heterodimeric glycoprotein with molecular mass of about 106 kDa. The protease hydrolyzes azocasein, fibrinogen and oxidized insulin B-chain. The enzyme readily hydrolyzes the Aalpha-chain and more slowly Bbeta-chain of fibrinogen. VLAIP does not cleave fibrin. The complete amino acid sequences of the two different monomers of VLAIP are deduced from the nucleotide sequences of cDNAs encoding these proteins. The full-length cDNA sequences of the VLAIP-A and VLAIP-B encode open reading frames of 616 and 614 amino acids that include signal peptide, propeptide and mature metalloproteinase with disintegrin-like and cysteine-rich domains. VLAIP belongs to the metalloprotease/disintegrin family of reprolysins and has high identity with the proteins that induce apoptosis of endothelial cells. Treatment of HUVEC cells with VLAIP induces changes in the attachment of cells to the substrate and causes cell death. We demonstrated that VLAIP inhibits endothelial cell adhesion to extracellular matrix proteins: fibrinogen, fibronectin, vitronectin, collagen I, and collagen IV. The induction of apoptosis by VLAIP was shown by means of a typical DNA fragmentation pattern of apoptotic cells as well as by monitoring phosphatidylserine externalization using annexin V-FITC staining and flow cytometric analysis. 相似文献
4.
CD44 is the main cellular receptor for hyaluronic acid (HA). We previously found that overexpression of CD44 inhibited tumor growth of mouse fibrosarcoma cells in mice. Here, we show that soluble recombinant CD44 HA-binding domain (CD44-HABD) acts directly onto endothelial cells by inhibiting endothelial cell proliferation in a cell-specific manner. Consequently, soluble recombinant CD44-HABD also blocked angiogenesis in vivo in chick and mouse, and thereby inhibited tumor growth of various origins at very low doses (0.25 mg/kg x day). The antiangiogenic effect of CD44 is independent of its HA-binding capacity, since mutants deficient in HA binding still maintain their antiangiogenic and antiproliferative properties. Recombinant CD44-HABD represents a novel class of angiogenesis inhibitors based on a cell-surface receptor. 相似文献
5.
The tumor suppressor CYLD interacts with TRIP and regulates negatively nuclear factor kappaB activation by tumor necrosis factor 总被引:5,自引:0,他引:5
Regamey A Hohl D Liu JW Roger T Kogerman P Toftgard R Huber M 《The Journal of experimental medicine》2003,198(12):1959-1964
Cylindromas are benign adnexal skin tumors caused by germline mutations in the CYLD gene. In most cases the second wild-type allele is lost in tumor tissue, suggesting that CYLD functions as tumor suppressor. CYLD is a protein of 956 amino acids harboring a functional deubiquitinating domain at the COOH-terminal end. To shed more light on the function of CYLD, we have performed a yeast two hybrid screen using an HaCaT cDNA library that identified the RING finger protein TRIP (TRAF-interacting protein) as interactor with full-length CYLD. Mapping of the interacting domains revealed that the central domain of CYLD binds to the COOH-terminal end of TRIP. Far Western analysis and coimmunoprecipitations in mammalian cells confirmed that full-length CYLD binds to the COOH-terminal domain of TRIP. Because TRIP is an inhibitor of nuclear factor (NF)-kappaB activation by tumor necrosis factor (TNF), the effect of CYLD on NF-kappaB activation was investigated in HeLa cells. The results established that CYLD down-regulates NF-kappaB activation by TNF-alpha. The inhibition by CYLD depends on the presence of the central domain interacting with TRIP and its deubiquitinating activity. These findings indicate that cylindromas arise through constitutive NF-kappaB activation leading to hyperproliferation and tumor growth. 相似文献
6.
Evelin Lätt Jarek Mäestu Triin Rääsk Daniela A. Rubin Priit Purge Meeli Saar Liina Utsal Jaak Jürimäe Katre Maasalu Toivo Jürimäe 《Zeitschrift fur Gesundheitswissenschaften》2013,21(3):231-239
Aim
The aim was to examine the associations between physical activity (PA) and cardiovascular fitness (CVF) and fatness in boys (age 12.04?±?0.77 year) and to assess if weight status influences these associations.Subjects and methods
Two hundred sixty-five boys participated in the study. PA was measured by accelerometry. Body fatness estimators included body mass index (BMI), body fat%, sum of five skinfolds and waist circumference. CVF was directly measured during stepwise incremental exercise test and expressed in peak oxygen uptake (VO2peak) and maximal power output (W max).Results
All measured PA levels (except vigorous PA in obese boys) were significant predictors of W max per kilogram of body mass in normal weight and obese boys. Vigorous PA, moderate-to-vigorous PA (MVPA), total PA in normal weight and vigorous PA in obese boys were significant predictors of W max. Variation in VO2peak per kilogram of body mass was significantly explained by moderate PA, vigorous PA, MVPA and total PA in normal weight only. For those of normal weight, vigorous PA, MVPA and total PA were negatively associated with body fat% and sum of five skinfolds. In obese boys, moderate PA and MVPA were negatively associated with BMI.Conclusions
Time spent in vigorous PA and MVPA was associated with fatness parameters in normal weight and obese boys and with CVF parameters only in normal weight boys. Normal weight boys spent more time in vigorous PA and MVPA than overweight and obese boys and had high values in VO2peak, VO2peak per kilogram of body mass and W max per kilogram of body mass.7.
In this study, the effect of rapidly increased training volume on performance, recovery-stress state and stress hormones over a six-day training camp were investigated in competitive male rowers (n=21). The training regimen consisted mainly of low-intensity on-water rowing and resistance training, in total 19.6+/-3.8 hrs, corresponding to approximately 100% increase in training load. Two thousand metre rowing ergometer performance time worsened by the end of a heavy training period. The resting blood testosterone decreased and cortisol remained unchanged. The Recovery-Stress-Questionnaire for Athletes (RESTQ-Sport) revealed an increase in somatic components of stress (Fatigue, Somatic Complaints, Fitness/Injury) and a decrease in recovery factors (Success, Social Relaxation, Sleep Quality, Being in Shape, Self-Efficacy). Relationships were observed between training volume, and Fatigue (r=0.49), Somatic Complaints (r=0.50) and Sleep Quality (r=-0.58) at the end of heavy training. In addition, relationships were also observed between cortisol and Fatigue (r=0.48) at the end of heavy training as well as between changes in cortisol and changes in Fatigue (r=0.57) and Social Stress (r=0.51). In conclusion, changes in specific stress and recovery scales of the RESTQ-Sport for athletes and changes in stress hormone values indicated a state of heavy training stress and incomplete recovery at the end of a six-day heavy training period. 相似文献
8.
Kousoulidou L Parkel S Zilina O Palta P Puusepp H Remm M Turner G Boyle J van Bokhoven H de Brouwer A Van Esch H Froyen G Ropers HH Chelly J Moraine C Gecz J Kurg A Patsalis PC 《European journal of medical genetics》2007,50(6):399-410
The rapid advancement of high-resolution DNA copy number assessment methods revealed the significant contribution of submicroscopic genetic imbalances to abnormal phenotypes, including mental retardation. In order to detect submicroscopic genetic imbalances, we have screened 20 families with X-linked mental retardation (XLMR) using a chromosome X-specific array-MAPH platform with median resolution of 238 kb. Among the 20 families, 18 were experimental, as they were not previously screened with any microarray method, and two were blind controls with known aberrations, as they were previously screened by array-CGH. This study presents the first clinical application of chromosome X-specific array-MAPH methodology. The screening of 20 affected males from 20 unrelated XLMR families resulted in the detection of an unknown deletion, spanning a region of 7–23 kb. Family studies and population screening demonstrated that the detected deletion is an unknown rare copy number variant. One of the control samples, carrying approximately 6-Mb duplication was correctly identified, moreover it was found to be interrupted by a previously unknown 19 kb region of normal copy number. The second control 50 kb deletion was not identified, as this particular region was not covered by array-MAPH probes. This study demonstrates that the chromosome X-specific array-MAPH platform is a valuable tool for screening patients with XLMR, or other X-linked disorders, and emerges the need for introducing new high-resolution screening methods for the detection of genetic imbalances. 相似文献
9.
Jürimäe J von Duvillard SP Mäestu J Cicchella A Purge P Ruosi S Jürimäe T Hamra J 《European journal of applied physiology》2007,101(3):341-346
The purpose of the present study was to investigate the use of electromyographic signals (EMG), to determine the EMG threshold (EMGT) in four lower extremity muscles and to compare these thresholds with the second ventilatory
threshold (VT2) in subjects participating in different sports and at different performance levels. Forty-nine subjects (23.8 ± 5.7 years,
182.7 ± 5.3 cm, 79.1 ± 8.6 kg) including eleven cyclists, ten team-handball players, nine kayakers, eight power lifters and
eleven controls were investigated utilizing a cycle ergometer. Respiratory gas exchange measures were collected and EMG activity
was continuously recorded from four muscles (vastus lateralis, vastus medialis, biceps femoris and gastrocnemius lateralis).
The VO2max averaged 56.1 ± 11.1 ml kg−1 min−1, the average aerobic power was 348.5 ± 61.0 W and the corresponding VT2 occurred at 271.4 ± 64.0 W. The EMGT ranged from
80 to 98% of power output for the different muscles. The VT2 and EMG thresholds from four different muscles were not different.
When thresholds were analyzed among different groups of subjects, no significant difference was observed between VT2 and EMGT despite threshold differences between the groups. All four EMGT
were significantly related to maximal aerobic power (r = 0.73–0.83) and were highly correlated to each other (r = 0.57–0.88). In conclusion, EMGT can be used to determine the VT2 for individuals independent of sport specificity or performance
level. 相似文献
10.
Overexpressed human CD44s promotes lung colonization during micrometastasis of murine fibrosarcoma cells: Facilitated retention in the lung vasculature
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Priit Kogerman Man-Sun Sy Lloyd A. Culp 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(24):13233-13238
Normally nonmetastatic murine sis-transformed BALB/c 3T3 cells, transfected with human CD44s gene (hCD44s), acquire spontaneous metastatic capacity to the lung. The mechanism(s) of this facilitated micrometastasis was analyzed in an experimental metastasis model. Human CD44s overexpression promoted the earliest stages severalfold (initial implantation and subsequent stabilization of tumor cells) but was irrelevant for later stages (subsequent outgrowth) of lung experimental micrometastasis. By injecting mixed populations of parental (nonmetastatic) and CD44s-transfected cells, it was shown that cell–cell adhesion between tumor and parental cells was not promoted by hCD44s but that promotion of cell–cell adhesion to lung endothelium or specifically between transfected cells (via hyaluronan) are likely mechanisms. Results obtained with hCD44s-negative primary tumor cells and hCD44s-positive or -negative variants of lung micrometastatic cells (after s.c. injection of transfectants) confirmed the importance of CD44s overexpression for early but not late stages of experimental lung metastasis. Therefore, CD44s represents a metastasis-facilitating molecule that is irrelevant for primary tumor outgrowth but that promotes micrometastasis to the lungs at the very earliest stages. 相似文献