scholarly journals Genetic variants and cognitive functions in patients with brain tumors

2019 ◽  
Vol 21 (10) ◽  
pp. 1297-1309 ◽  
Author(s):  
Denise D Correa ◽  
Jaya Satagopan ◽  
Axel Martin ◽  
Erica Braun ◽  
Maria Kryza-Lacombe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dna Repair ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Cell Cycle Regulation ◽  
Cognitive Outcome ◽  
Cholesterol Transport ◽  
Tumor Patients ◽  
Cycle Regulation

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.

scholarly journals Focus-ING on DNA Integrity: Implication of ING Proteins in Cell Cycle Regulation and DNA Repair Modulation

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 58
Author(s):  
Jérôme Archambeau ◽  
Alice Blondel ◽  
Rémy Pedeux
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Chromatin Remodeling ◽  
Tumor Suppressor Genes ◽  
Cell Cycle Regulation ◽  
Genomic Stability ◽  
Dna Integrity ◽  
Damage Response ◽  
The Stability ◽  
Cycle Regulation

The ING family of tumor suppressor genes is composed of five members (ING1-5) involved in cell cycle regulation, DNA damage response, apoptosis and senescence. All ING proteins belong to various HAT or HDAC complexes and participate in chromatin remodeling that is essential for genomic stability and signaling pathways. The gatekeeper functions of the INGs are well described by their role in the negative regulation of the cell cycle, notably by modulating the stability of p53 or the p300 HAT activity. However, the caretaker functions are described only for ING1, ING2 and ING3. This is due to their involvement in DNA repair such as ING1 that participates not only in NERs after UV-induced damage, but also in DSB repair in which ING2 and ING3 are required for accumulation of ATM, 53BP1 and BRCA1 near the lesion and for the subsequent repair. This review summarizes evidence of the critical roles of ING proteins in cell cycle regulation and DNA repair to maintain genomic stability.

scholarly journals Cell cycle regulation of human DNA repair and chromatin remodeling genes

DNA Repair ◽  
2015 ◽  
Vol 30 ◽  
pp. 53-67 ◽  
Author(s):  
Robin Mjelle ◽  
Siv Anita Hegre ◽  
Per Arne Aas ◽  
Geir Slupphaug ◽  
Finn Drabløs ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Chromatin Remodeling ◽  
Cell Cycle Regulation ◽  
Human Dna ◽  
Cycle Regulation

SP-02: Cell Cycle Regulation of the DNA Damage Response: Targeting WEE1 Kinase to Impair DNA Repair.

2012 ◽  
Vol 104 ◽  
pp. 21
Author(s):  
M.A.T.M. Van Vugt ◽  
M. Krajewska ◽  
H. Sillje ◽  
A.M. Heijink ◽  
Y. Bisselink ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Cell Cycle Regulation ◽  
Damage Response ◽  
Wee1 Kinase ◽  
Cycle Regulation

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

2009 ◽  
Vol 43 (10) ◽  
pp. 985-994 ◽  
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

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

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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