Expression profiles are different in carbon ion-irradiated normal human fibroblasts and their bystander cells

Sir2 is a NAD+-dependent protein deacetylase that extends lifespan in yeast and worms. This study examines seven human proteins homologous to Sir2 (SIRT1 through SIRT7) for cellular localization, expression profiles, protein deacetylation activity, and effects on human cell lifespan. We found that: 1) three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7) show different subnuclear localizations: SIRT6 and SIRT7 are associated with heterochromatic regions and nucleoli, respectively, where yeast Sir2 functions; 2) SIRT3, SIRT4, and SIRT5 are localized in mitochondria, an organelle that links aging and energy metabolism; 3) cellular p53 is a major in vivo substrate of SIRT1 deacetylase, but not the other six SIRT proteins; 4) SIRT1, but not the other two nuclear SIRT proteins, shows an in vitro deacetylase activity on histone H4 and p53 peptides; and 5) overexpression of any one of the seven SIRT proteins does not extend cellular replicative lifespan in normal human fibroblasts or prostate epithelial cells. This study supports the notion that multiple human SIRT proteins have evolutionarily conserved and nonconserved functions at different cellular locations and reveals that the lifespan of normal human cells, in contrast to that of lower eukaryotes, cannot be manipulated by increased expression of a single SIRT protein.

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Temporally distinct response of irradiated normal human fibroblasts and their bystander cells to energetic heavy ions

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/j.mrfmmm.2007.11.001 ◽

2008 ◽

Vol 639 (1-2) ◽

pp. 35-44 ◽

Cited By ~ 42

Author(s):

Nobuyuki Hamada ◽

Meinan Ni ◽

Tomoo Funayama ◽

Tetsuya Sakashita ◽

Yasuhiko Kobayashi

Keyword(s):

Heavy Ions ◽

Human Fibroblasts ◽

Normal Human ◽

Bystander Cells

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Gene Expression Profiles of Normal Human Fibroblasts after Exposure to Ionizing Radiation: A Comparative Study of Low and High Doses

Radiation Research ◽

10.1667/rr3354 ◽

2005 ◽

Vol 164 (1) ◽

pp. 17-26 ◽

Cited By ~ 148

Author(s):

Liang-Hao Ding ◽

Masato Shingyoji ◽

Fanqing Chen ◽

Jeng-Jong Hwang ◽

Sandeep Burma ◽

...

Keyword(s):

Gene Expression ◽

Ionizing Radiation ◽

Comparative Study ◽

Expression Profiles ◽

Human Fibroblasts ◽

Gene Expression Profiles ◽

Normal Human ◽

High Doses

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Precursor-Boosted Production of Metabolites in Nasturtium officinale Microshoots Grown in Plantform Bioreactors, and Antioxidant and Antimicrobial Activities of Biomass Extracts

Molecules ◽

10.3390/molecules26154660 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4660

Author(s):

Marta Klimek-Szczykutowicz ◽

Michał Dziurka ◽

Ivica Blažević ◽

Azra Đulović ◽

Małgorzata Miazga-Karska ◽

...

Keyword(s):

Photosynthetic Pigments ◽

Human Fibroblasts ◽

Antimicrobial Activities ◽

Precursor Feeding ◽

Nasturtium Officinale ◽

Qualitative And Quantitative ◽

Normal Human ◽

Inhibition Zones ◽

Ferulic Acids ◽

Antioxidant And Antimicrobial Activities

The study demonstrated the effects of precursor feeding on the production of glucosinolates (GSLs), flavonoids, polyphenols, saccharides, and photosynthetic pigments in Nasturtium officinale microshoot cultures grown in Plantform bioreactors. It also evaluated the antioxidant and antimicrobial activities of extracts. L-phenylalanine (Phe) and L-tryptophan (Trp) as precursors were tested at 0.05, 0.1, 0.5, 1.0, and 3.0 mM. They were added at the beginning (day 0) or on day 10 of the culture. Microshoots were harvested after 20 days. Microshoots treated with 3.0 mM Phe (day 0) had the highest total GSL content (269.20 mg/100 g DW). The qualitative and quantitative profiles of the GSLs (UHPLC-DAD-MS/MS) were influenced by precursor feeding. Phe at 3.0 mM stimulated the best production of 4-methoxyglucobrassicin (149.99 mg/100 g DW) and gluconasturtiin (36.17 mg/100 g DW). Total flavonoids increased to a maximum of 1364.38 mg/100 g DW with 3.0 mM Phe (day 0), and polyphenols to a maximum of 1062.76 mg/100 g DW with 3.0 mM Trp (day 0). The precursors also increased the amounts of p-coumaric and ferulic acids, and rutoside, and generally increased the production of active photosynthetic pigments. Antioxidant potential increased the most with 0.1 mM Phe (day 0) (CUPRAC, FRAP), and with 0.5 mM Trp (day 10) (DPPH). The extracts of microshoots treated with 3.0 mM Phe (day 0) showed the most promising bacteriostatic activity against microaerobic Gram-positive acne strains (MIC 250–500 µg/mL, 20–21 mm inhibition zones). No extract was cytotoxic to normal human fibroblasts over the tested concentration range (up to 250 μg/mL).

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