FOXO Transcription Factors in Cell-Cycle Regulation and the Response to Oxidative Stress

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.

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A new role for plant R2R3-MYB transcription factors in cell cycle regulation

Cell Research ◽

10.1038/cr.2009.123 ◽

2009 ◽

Vol 19 (11) ◽

pp. 1231-1232 ◽

Cited By ~ 34

Author(s):

Eleonora Cominelli ◽

Chiara Tonelli

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Cell Cycle Regulation ◽

Myb Transcription Factors ◽

R2r3 Myb ◽

Cycle Regulation ◽

R2r3 Myb Transcription Factors

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Oxidative stress-induced DNA damage and cell cycle regulation in B65 dopaminergic cell line

Free Radical Research ◽

10.1080/10715760903159188 ◽

2009 ◽

Vol 43 (10) ◽

pp. 985-994 ◽

Cited By ~ 32

Author(s):

Javier G. Pizarro ◽

Jaume Folch ◽

Aurelio Vazquez De la Torre ◽

Ester Verdaguer ◽

Felix Junyent ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Dna Damage ◽

Cell Line ◽

Cell Cycle Regulation ◽

Dopaminergic Cell ◽

Cycle Regulation

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G1 Transcription Factors Are Differentially Regulated in Saccharomyces cerevisiae by the Swi6-Binding Protein Stb1

Molecular and Cellular Biology ◽

10.1128/mcb.23.14.5064-5077.2003 ◽

2003 ◽

Vol 23 (14) ◽

pp. 5064-5077 ◽

Cited By ~ 45

Author(s):

Michael Costanzo ◽

Oliver Schub ◽

Brenda Andrews

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Transcription Factors ◽

Transcriptional Activation ◽

Chromatin Immunoprecipitation ◽

Cell Cycle Regulation ◽

Binding Protein ◽

Microarray Studies ◽

Cycle Regulation ◽

Integral Feature

ABSTRACT Stage-specific transcriptional programs are an integral feature of cell cycle regulation. In the budding yeast Saccharomyces cerevisiae, over 120 genes are coordinately induced in late G1 phase by two heterodimeric transcription factors called SBF and MBF. Activation of SBF and MBF is an upstream initiator of key cell cycle events, including budding and DNA replication. SBF and MBF regulation is complex and genetically redundant, and the precise mechanism of G1 transcriptional activation is unclear. Assays using SBF- and MBF-specific reporter genes revealed that the STB1 gene specifically affected MBF-dependent transcription. STB1 encodes a known Swi6-binding protein, but an MBF-specific function had not been previously suspected. Consistent with a specific role in regulating MBF, a STB1 deletion strain requires SBF for viability and microarray studies show a decrease in MBF-regulated transcripts in a swi4Δ mutant following depletion of Stb1. Chromatin immunoprecipitation experiments confirm that Stb1 localizes to promoters of MBF-regulated genes. Our data indicate that, contrary to previous models, MBF and SBF have unique components and might be distinctly regulated.

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A System-Based Comparison of Gene Expression Reveals Alterations in Oxidative Stress, Disruption of Ubiquitin-Proteasome System and Altered Cell Cycle Regulation after Exposure to Cadmium and Methylmercury in Mouse Embryonic Fibroblast

Toxicological Sciences ◽

10.1093/toxsci/kfq003 ◽

2010 ◽

Vol 114 (2) ◽

pp. 356-377 ◽

Cited By ~ 37

Author(s):

Xiaozhong Yu ◽

Joshua F. Robinson ◽

Jaspreet S. Sidhu ◽

Sungwoo Hong ◽

Elaine M. Faustman

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Cell Cycle ◽

Cell Cycle Regulation ◽

Ubiquitin Proteasome System ◽

Mouse Embryonic Fibroblast ◽

Ubiquitin Proteasome ◽

Altered Cell ◽

Cycle Regulation ◽

Embryonic Fibroblast

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77 Nobiletin supplementation affects gene expression profiles of the Akt pathway in bovine embryos invitro

Reproduction Fertility and Development ◽

10.1071/rdv32n2ab77 ◽

2020 ◽

Vol 32 (2) ◽

pp. 164

Author(s):

Y. N. Cajas ◽

K. Cañón-Beltrán ◽

C. L. V. Leal ◽

M. E. González ◽

A. Gutierrez-Adán ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Cell Cycle ◽

Embryonic Development ◽

Cell Cycle Regulation ◽

Akt Pathway ◽

Cleavage Rate ◽

Cell Stage ◽

Cycle Regulation ◽

And Oxidative Stress

Embryonic genome activation (EGA) is a critical event in early embryonic development and occurs in 8-16-cell stage embryos in bovine. Invitro embryo production increases reactive oxygen species (ROS), leading to low yield and cell death. Nobiletin is an antioxidant that inhibits ROS production and affects cell cycle regulation. The aim of this study was to evaluate the effect of nobiletin supplementation in two key periods of early embryo development on blastocyst yield and expression of candidate genes of the Akt pathway. Invitro-produced zygotes were cultured in synthetic oviductal fluid supplemented with 5% FCS (control; C); C with 5 or 10 µM nobiletin (MedChemExpress; N5, N10) or C with 0.03% dimethyl sulfoxide (CD vehicle for nobiletin dilution) during the minor (2-8-cell stage; MNEGA) or major (8-16-cell stage; MJEGA) phase of EGA, considered as two separate experiments. For all groups, the speed of development was considered, and normally developing embryos that reach ≥8 cells at 54h post-insemination and ≥16 cells at 96h post-insemination were selected and cultured in control medium until Day 8, respectively. Embryos at ≥8-cell stage (N5/N10 MNEGA), 16-cell stage (N5/N10MJEGA), and Day 7 blastocysts of both periods were snap-frozen in LN2 for gene expression analysis. Cleavage rate and blastocyst yield (Day 7-8) were evaluated. The mRNA abundance of candidate genes related to the Akt pathway (CDK2, PGC1A, PPARG, RPS6KB1) and oxidative stress (GPX1) was measured by quantitative PCR. The H2AFZ and ACTB genes were used as housekeeping genes. Statistical analysis was assessed by one-way ANOVA. Nobiletin supplementation during MNEGA showed no differences in cleavage rate, whereas the blastocyst yield at Day 8 was higher (P<0.001) for N5 (42.9±1.4%) and N10 (45.3±2.1%) compared with C (32.9±1.1%) and CD (32.6±1.4%) groups. When nobiletin was supplemented during MJEGA, no differences were found in cleavage rate; however, Day 8 blastocyst yield was higher (P<0.001) for N10 (61.8±0.7%) compared with C (45.2±1.7%), CD (43.6±1.4%), and N5 (52.1±2.1%) groups, whereas N5 was higher (P<0.05) compared with both control groups. The mRNA abundance of CDK2 significantly increases in 8-cell stage embryos from N5 and N10 groups during MNEGA, whereas 16-cell stage embryos from N10 group during MJEGA showed a significant increase compared with both controls (P<0.05). The expression of PGC1A was significantly higher in blastocysts from N5, N10 during MNEGA, and N10 during MJEGA groups compared with both controls (P<0.05). No differences were observed for PPARG and RPS6KB1 in any group from both phases. GPX1, an oxidative indicator gene, was up-regulated in all nobiletin-supplemented groups from both phases compared with controls (P<0.05). In conclusion, supplementation of embryo culture during MNEGA or MJEGA with nobiletin improves embryo development and induces changes in the transcriptional genes related to cell cycle regulation and oxidative stress. This suggests that nobiletin acts through the Akt pathway during the first stages of embryonic development. Funding was provided by MINECO-Spain AGL2015-70140-R&RTI2018-093548-B-I00; Y. N. Cajas, SENESCYT-Ecuador; C. L. V. Leal, FAPESP-Brasil 2017/20339-3.

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