Cell Line

Publication Title: 
Oncogene

Cell cycle checkpoints and tumor suppressor gene functions appear to be required for the maintenance of a stable genome in proliferating cells. In this study chromosomal destabilization was monitored in relation to telomere structure, lifespan control and G2 checkpoint function. Replicative senescence was inactivated in secondary cultures of human skin fibroblasts by expressing the human papillomavirus type 16 (HPV-16) E6 oncoprotein to inactivate p53. Chromosome aberrations were enumerated during in vitro aging of isogenic control (F5neo) and HPV-16E6-expressing (F5E6) fibroblasts.

Author(s): 
Filatov, L.
Golubovskaya, V.
Hurt, J. C.
Byrd, L. L.
Phillips, J. M.
Kaufmann, W. K.
Publication Title: 
The EMBO journal

The yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity. Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms. Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation.

Author(s): 
Langley, Emma
Pearson, Mark
Faretta, Mario
Bauer, Uta-Maria
Frye, Roy A.
Minucci, Saverio
Pelicci, Pier Giuseppe
Kouzarides, Tony
Publication Title: 
Biogerontology

Normal human cells have a finite proliferative potential in vitro. However, some DNA viral proteins, such as SV40 Tg, can alter this and extend the lifespan after which the cells enter crisis, a period when massive cell death occurs. Based on these observations, a two-stage model for cellular senescence has been proposed with a distinct function for each stage.

Author(s): 
Rubelj, Ivica
Huzak, Miljenko
Brdar, Branko
Pereira-Smith, Olivia M.
Publication Title: 
Experimental Cell Research

Numerous studies have shown that supplementation of the growth medium of human fibroblasts with dexamethasone at physiologic concentrations extends replicative lifespan up to 30%. While this extension of lifespan has been used to probe various aspects of the senescent phenotype, no mechanism for the increased lifespan of human fibroblasts grown in the presence of dexamethasone has ever been identified.

Author(s): 
Mawal-Dewan, Madhu
Frisoni, Lorenza
Cristofalo, Vincent J.
Sell, Christian
Publication Title: 
The Biochemical Journal

NaCT (sodium-coupled citrate transporter) is an Na(+)-coupled citrate transporter identified recently in mammals that mediates the cellular uptake of citrate. It is expressed predominantly in the liver. NaCT is structurally and functionally related to the product of the Indy (I'm not dead yet) gene in Drosophila, the dysfunction of which leads to lifespan extension. Here, we show that NaCT mediates the utilization of extracellular citrate for fat synthesis in human liver cells, and that the process is stimulated by lithium.

Author(s): 
Inoue, Katsuhisa
Zhuang, Lina
Maddox, Dennis M.
Smith, Sylvia B.
Ganapathy, Vadivel
Publication Title: 
Investigative Ophthalmology & Visual Science

PURPOSE: To investigate the migratory and contractile behavior of isolated human corneal fibroblasts in fibrillar collagen matrices. METHODS: A telomerase-infected, extended-lifespan human corneal fibroblast cell line (HTK) was transfected by using a vector for enhanced green fluorescent protein (GFP)-alpha-actinin. Cells were plated at low density on top of or within 100-microm-thick fibrillar collagen lattices. After 18 hours to 7 days, time-lapse imaging was performed.

Author(s): 
Vishwanath, Mridula
Ma, Lisha
Otey, Carol A.
Jester, James V.
Petroll, W. Matthew
Publication Title: 
Nature

Calorie restriction extends lifespan in organisms ranging from yeast to mammals. In yeast, the SIR2 gene mediates the life-extending effects of calorie restriction. Here we show that the mammalian SIR2 orthologue, Sirt1 (sirtuin 1), activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes. Upon food withdrawal Sirt1 protein binds to and represses genes controlled by the fat regulator PPAR-gamma (peroxisome proliferator-activated receptor-gamma), including genes mediating fat storage.

Author(s): 
Picard, FrÈdÈric
Kurtev, Martin
Chung, Namjin
Topark-Ngarm, Acharawan
Senawong, Thanaset
Machado De Oliveira, Rita
Leid, Mark
McBurney, Michael W.
Guarente, Leonard
Publication Title: 
The EMBO journal

Telomere shortening in normal human cells causes replicative senescence, a p53-dependent growth arrest state, which is thought to represent an innate defence against tumour progression. However, although it has been postulated that critical telomere loss generates a 'DNA damage' signal, the signalling pathway(s) that alerts cells to short dysfunctional telomeres remains only partially defined.

Author(s): 
Gire, VÈronique
Roux, Pierre
Wynford-Thomas, David
Brondello, Jean-Marc
Dulic, Vjekoslav
Publication Title: 
Blood

To obtain the large amount of T cells required for adoptive immunotherapy in a clinical setting, T-cell lifespan extension by human telomerase reverse transcriptase (hTERT) transduction is of particular interest. However, constitutive expression of hTERT is associated with malignant transformation and thus warrants a detailed evaluation of the safety of hTERT-transduced T cells before clinical application.

Author(s): 
Schreurs, Marco W. J.
Hermsen, Mario A. J. A.
Geltink, Ramon I. Klein
Scholten, Kirsten B. J.
Brink, Antoinette A. T. P.
Kueter, Esther W. M.
Tijssen, Marianne
Meijer, Chris J. L. M.
Ylstra, Bauke
Meijer, Gerrit A.
Hooijberg, Erik
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

In investigating the role of metal ions in the pathogenesis of Huntington's disease, we examined the effects of clioquinol, a metal-binding compound currently in clinical trials for Alzheimer's disease treatment, on mutant huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine-expanded huntingtin exon 1 accumulated less mutant protein and showed decreased cell death when treated with clioquinol. This effect was polyglutamine-length-specific and did not alter mRNA levels or protein degradation rates.

Author(s): 
Nguyen, Trent
Hamby, Aaron
Massa, Stephen M.

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