scholarly journals HIV-1 gp120 and morphine induced oxidative stress: role in cell cycle regulation

2015 ◽  
Vol 6 ◽  
Author(s):  
Thangavel Samikkannu ◽  
Deepa Ranjith ◽  
Kurapati V. K. Rao ◽  
Venkata S. R. Atluri ◽  
Emely Pimentel ◽  
...  
2019 ◽  
Vol 21 (10) ◽  
pp. 1297-1309 ◽  
Author(s):  
Denise D Correa ◽  
Jaya Satagopan ◽  
Axel Martin ◽  
Erica Braun ◽  
Maria Kryza-Lacombe ◽  
...  

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.


2009 ◽  
Vol 43 (10) ◽  
pp. 985-994 ◽  
Author(s):  
Javier G. Pizarro ◽  
Jaume Folch ◽  
Aurelio Vazquez De la Torre ◽  
Ester Verdaguer ◽  
Felix Junyent ◽  
...  

2020 ◽  
Vol 32 (2) ◽  
pp. 164
Author(s):  
Y. N. Cajas ◽  
K. Cañón-Beltrán ◽  
C. L. V. Leal ◽  
M. E. González ◽  
A. Gutierrez-Adán ◽  
...  

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.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi208-vi208
Author(s):  
Gabriel Valentín Guillama ◽  
Lilia Kucheryavykh

Abstract Patients infected with human immunodeficiency virus type 1 (HIV-1) are more prone to developing cancers, including glioblastomas (GBMs). The median survival for GBM patients with HIV is significantly shorter than for HIV-negative GBM patients, even though they receive the same treatments. This difference indicates that HIV infection is associated with more aggressive tumor behavior and with treatment resistance. Earlier we demonstrated that gp120, a main glycoprotein in the HIV shell, stimulates glycolysis and protein synthesis in glioma cells. The purpose of this study was to evaluate the underlying gp120 dependent signaling mechanism in glioma cell. Mouse glioma cells GL-261 were continuously cultured for 7 days in medium with and without soluble gp120 Bal III (100ng/ml) and collected for Western blot and Cell cycle assays. Western blot analysis presented an increase in phosphorylation of Proline-rich tyrosine kinase (Pyk2(Y402)), p38(YT100/Y182) and p70s6(T421/S424), the key proteins of the Pyk2 pathway, along with the increased levels of Akt(S473) and Glycogen Synthase Kinase 3b (GSK3b (S9)) phosphorylation. Flow cytometry analysis of Cell Cycle revealed an increase of G2/M phase in cells cultured in gp120 Bal III when compared to control cells. Furthermore, GL-261 cells with knock-out of Pyk2 via CRISPR Cas 9 gene editing showed no significant change in cell cycle regulation when cultured with gp120 Bal III.Overall, these results demonstrate that gp120 triggers activation of Pyk2/MAPK and Akt/GSK3b pathways and alter cell cycle regulation in GBM. This research was made possible by NIH grant number 1SC1GM122691.


2012 ◽  
Vol 28 (11) ◽  
pp. 897-902 ◽  
Author(s):  
Hiroshi Shigetomi ◽  
Yumi Higashiura ◽  
Hirotaka Kajihara ◽  
Hiroshi Kobayashi

2010 ◽  
Vol 174 (5) ◽  
pp. 582-589 ◽  
Author(s):  
Vincent J. Caiozzo ◽  
Erich Giedzinski ◽  
Mike Baker ◽  
Tatiana Suarez ◽  
Atefeh Izadi ◽  
...  

2005 ◽  
Vol 7 (5-6) ◽  
pp. 752-760 ◽  
Author(s):  
Yoko Furukawa-Hibi ◽  
Yosuke Kobayashi ◽  
Chen Chen ◽  
Noboru Motoyama

2020 ◽  
Author(s):  
Jiawei Wu ◽  
Xuelong Zhang ◽  
Kaili Wang ◽  
Lidan Xu ◽  
Bangquan Liu ◽  
...  

Abstract Background MSM has a high risk of HIV infection. Previous studies showed that the cell cycle regulation played an important role in HIV-1 infection, especially in G2/M checkpoint. The ATR, Chk1, Cdc25C and CDK1 are key genes in G2/M checkpoint. However, the association between the SNPs of these genes and susceptibility to HIV-1 infection and AIDS progression remains unknown. Results 42 tSNPs of G2/M checkpoint genes were genotyped to analyze the association between these tSNPs and susceptibility to HIV-1 infection and AIDS progression among MSM (529 HIV − 1 seropositive men and 529 HIV-1 seronegative men) in northern China. The results showed that rs34660854-A and rs75368165-A in ATR gene and rs3756766-A in Cdc25C gene could increase the risk of HIV-1 infection (P = 0.049, P = 0.020 and P = 0.010, respectively), and ATR rs75069062 and Chk1 rs10893405 were significantly associated with AIDS progression (P = 0.026 and P = 0.029, respectively). Besides, rs34660854 and rs75368165 in ATR gene, rs12576279 and rs540436 in Chk1 gene, rs3756766 in Cdc25C gene and rs139245206 in CDK1 gene were significantly associated with HIV-1 infection under different models (P < 0.05). Conclusions The genetic variants of G2/M checkpoint genes had a molecular impact on the genesis of HIV-1 infection and AIDS progression in northern Chinese MSM population.


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