ArticleFree radical biology & medicine2009
Early onset senescence occurs when fibroblasts lack the glutamate-cysteine ligase modifier subunit.
Article in Free radical biology & medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Multitarget Pharmacology of Sulfur-Nitrogen Heterocycles: Anticancer and Antioxidant Perspectives.Antioxidants (Basel, Switzerland) · 2024Review
- Critical Roles of the Cysteine-Glutathione Axis in the Production of γ-Glutamyl Peptides in the Nervous System.International journal of molecular sciences · 2023Review
- The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence.Antioxidants (Basel, Switzerland) · 2022Review
- Hydrogen sulfide (HaBIOTECH · 2021Review
- Oxidative Stress in Cancer.Cancer cell · 2020Review
- Hydrogen sulfide increases glutathione biosynthesis, and glucose uptake and utilisation in CFree radical research · 2018Article
- Loss of IκB kinase β promotes myofibroblast transformation and senescence through activation of the ROS-TGFβ autocrine loop.Protein & cell · 2016Article
- A Glutathione-Nrf2-Thioredoxin Cross-Talk Ensures Keratinocyte Survival and Efficient Wound Repair.PLoS genetics · 2016Article
- Focus on molecular events in the anterior chamber leading to glaucoma.Cellular and molecular life sciences : CMLS · 2014Review
- Microglia change from a reactive to an age-like phenotype with the time in culture.Frontiers in cellular neuroscience · 2014Article
- Impaired glutathione synthesis in neurodegeneration.International journal of molecular sciences · 2013Review
- Glutathione defense mechanism in liver injury: insights from animal models.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2013Review
- Unveiling the roles of the glutathione redox system in vivo by analyzing genetically modified mice.Journal of clinical biochemistry and nutrition · 2011Article
- Ultraviolet radiation: cellular antioxidant response and the role of ocular aldehyde dehydrogenase enzymes.Eye & contact lens · 2011Review
- Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress.Journal of toxicology · 2011Article
- Antioxidant defenses in the ocular surface.The ocular surface · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Cellular senescence is the irreversible entry of cells into growth arrest. Senescence of primary cells in culture has long been used as an in vitro model for aging. Glutamate-cysteine ligase (GCL) controls the synthetic rate of the important cellular antioxidant glutathione (GSH). The catalytic subunit of GCL, GCLC, is catalytically active and essential for life. By contrast the modifier subunit of GCL, GCLM, is dispensable in mice. Although it is recognized that GCLM increases the rate of GSH synthesis, its physiological role is unclear. Herein, we show that loss of Gclm leads to premature senescence of primary murine fibroblasts as characterized by: (a) diminished growth rate, (b) cell morphology consistent with senescence, (c) increases in senescence-associated beta-galactosidase activity, and (d) cell cycle arrest at the G(1)/S and G(2)/M boundaries. These changes are accompanied by increased intracellular ROS, accumulation of DNA damage, and induction of p53 and p21 proteins. We also found that N-acetylcysteine increases intracellular GSH and prevents premature senescence in Gclm(-/-) cells. These results suggest that the control of GCLM, which in turn controls aspects of the cellular redox environment via GSH, is important in determining the replicative capacity of the cell.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.