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Isc1p plays a key r...
Isc1p plays a key role in hydrogen peroxide resistance and chronological lifespan through modulation of iron levels and apoptosis.
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Almeida, Teresa (author)
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Marques, Marta (author)
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- Mojzita, Dominik, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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Amorim, Maria A (author)
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Silva, Rui D (author)
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Almeida, Bruno (author)
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Rodrigues, Pedro (author)
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Ludovico, Paula (author)
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- Hohmann, Stefan, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för cell- och molekylärbiologi,Department of Cell and Molecular Biology,University of Gothenburg
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Moradas-Ferreira, Pedro (author)
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Côrte-Real, Manuela (author)
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Costa, Vítor (author)
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(creator_code:org_t)
- 2008
- 2008
- English.
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In: Molecular biology of the cell. - 1939-4586. ; 19:3, s. 865-76
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Almeida, Teresa
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Marques, Marta
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Mojzita, Dominik ...
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Amorim, Maria A
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Silva, Rui D
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Almeida, Bruno
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show more...
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Rodrigues, Pedro
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Ludovico, Paula
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Hohmann, Stefan, ...
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Moradas-Ferreira ...
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Côrte-Real, Manu ...
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Costa, Vítor
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
- Articles in the publication
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Molecular biolog ...
- By the university
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University of Gothenburg
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Chalmers University of Technology