| 1. |
- Almeida, Teresa, et al.
(författare)
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Isc1p plays a key role in hydrogen peroxide resistance and chronological lifespan through modulation of iron levels and apoptosis.
- 2008
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Ingår i: Molecular biology of the cell. - 1939-4586. ; 19:3, s. 865-76
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Tidskriftsartikel (refereegranskat)abstract
- The inositolphosphosphingolipid phospholipase C (Isc1p) of Saccharomyces cerevisiae belongs to the family of neutral sphingomyelinases that generates the bioactive sphingolipid ceramide. In this work the role of Isc1p in oxidative stress resistance and chronological lifespan was investigated. Loss of Isc1p resulted in a higher sensitivity to hydrogen peroxide that was associated with an increase in oxidative stress markers, namely intracellular oxidation, protein carbonylation, and lipid peroxidation. Microarray analysis showed that Isc1p deficiency up-regulated the iron regulon leading to increased levels of iron, which is known to catalyze the production of the highly reactive hydroxyl radicals via the Fenton reaction. In agreement, iron chelation suppressed hydrogen peroxide sensitivity of isc1Delta mutants. Cells lacking Isc1p also displayed a shortened chronological lifespan associated with oxidative stress markers and aging of parental cells was correlated with a decrease in Isc1p activity. The analysis of DNA fragmentation and caspase-like activity showed that Isc1p deficiency increased apoptotic cell death associated with oxidative stress and aging. Furthermore, deletion of Yca1p metacaspase suppressed the oxidative stress sensitivity and premature aging phenotypes of isc1Delta mutants. These results indicate that Isc1p plays an important role in the regulation of cellular redox homeostasis, through modulation of iron levels, and of apoptosis.
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| 2. |
- Marques, Marta, et al.
(författare)
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The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae
- 2006
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Ingår i: Microbiology. - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 152:12, s. 3595-3605
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Tidskriftsartikel (refereegranskat)abstract
- Turnover of damaged molecules is considered to play a key role in housekeeping of cells exposed to oxidative stress, and during the progress of ageing. In this work, global changes in the transcriptome were analysed during recovery of yeast cells after H2O2 stress. Regarding induced genes, those associated with protein fate were the most significantly over-represented. In addition to genes encoding subunits of the 20S proteasome, genes related to vacuolar proteolysis (PEP4 and LAP4), protein sorting into the vacuole, and vacuolar fusion were found to be induced. The upregulation of PEP4 gene expression was associated with an increase in Pep4p activity. The induction of genes related to proteolysis was correlated with an increased protein turnover after H2O2-induced oxidation. Furthermore, protein degradation and the removal of oxidized proteins decreased in Pep4p-deficient cells. Pep4p activity also increased during chronological ageing, and cells lacking Pep4p displayed a shortened lifespan associated with higher levels of carbonylated proteins. PEP4 overexpression prevented the accumulation of oxidized proteins, but did not increase lifespan. These results indicate that Pep4p is important for protein turnover after oxidative damage; however, increased removal of oxidized proteins is not sufficient to enhance lifespan
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| 3. |
- Melo, Joao, et al.
(författare)
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Surgery for atrial fibrillation in patients with mitral valve disease: results at five years from the International Registry of Atrial Fibrillation Surgery.
- 2008
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Ingår i: The Journal of thoracic and cardiovascular surgery. - : Elsevier BV. - 1097-685X .- 0022-5223. ; 135:4, s. 863-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We sought to assess the clinical and survival benefit of atrial fibrillation surgery in patients submitted to mitral valve surgery after stabilization of postoperative rhythm at 1 year. METHODS: One thousand seven hundred twenty-three patients were enrolled. Patients with follow-up of longer than 1 year (n = 972) were divided into 3 groups according to surface electrocardiographic rhythm during follow-up visits: stable sinus rhythm, stable atrial fibrillation, and intermittent rhythms. Adverse cardiac event incidence and predictors of long-term outcome were compared among the 3 groups. RESULTS: In-hospital mortality was 2.6%. Risk factors for mortality were the cut-and-sew technique (odds ratio, 8.92; 95% confidence interval, 1.71-46.50; P = .009) and isolated left atrial procedure (odds ratio, 0.16; 95% confidence interval, 0.04-0.56; P = .004). At 1 year, 63.4% patients were in stable sinus rhythm. Stable sinus rhythm was found to be associated with early and late survival (P = .01, log-rank analysis). Multivariate binary logistic regression analysis found that left atrial dimension (odds ratio, 0.97; 95% confidence interval, 0.96-0.99; P = .005) and concomitant coronary revascularization (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P = .027) were independent predictors of stable sinus rhythm at 1 year after surgical intervention. At 48 months' follow-up, predictors for stable sinus rhythm were biatrial surgical approach and absence of preoperative permanent atrial fibrillation (odds ratio, 3.56; 95% confidence interval, 1.62-7.83; P < .002). Left atrial size (each millimeter) has a borderline statistical significance (odds ratio, 0.97; 95% confidence interval, 0.93-1.00; P = .065). Thromboembolic events were found to be associated with absence of stable sinus rhythm (P = .010, log-rank analysis). CONCLUSIONS: The achievement of stable sinus rhythm is a predictor of better survival and lower incidence of thromboembolic events. Predictors of stable sinus rhythm were smaller dimensions of the left atrium, biatrial approach, absence of preoperative permanent atrial fibrillation, and absence of concomitant coronary artery bypass grafting.
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