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Redox regulation of metabolic and signaling pathways by thioredoxin and glutaredoxin in NOS-3 overexpressing hepatoblastoma cells.

González R, López-Grueso MJ, Muntané J, Bárcena JA, Padilla CA - Redox Biol (2015)

Bottom Line: The aim of this study was to ascertain whether Trx and/or Grx systems mediate the antiproliferative effect of NO on hepatoblastoma cells by modulating the redox-state of key proteins.Silencing of Trx1 and Grx1 neutralized the increases in CD95, Akt1 and pAkt levels induced by NO and produced a marked increase in caspase-3 and -8 activities in both control and NOS-3 overexpressing cells concomitant with a decrease in the number of cells.These results demonstrate that the antiproliferative effect of NO is actually hampered by Trx1 and Grx1 and support the strategy of weakening the thiolic antioxidant defenses when designing new antitumoral therapies.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain. Electronic address: raulangello@hotmail.com.

No MeSH data available.


Related in: MedlinePlus

High levels of nitric oxide induced activity and expression of redox proteins. Trx activity (A) and Trx1 protein expression (B), Grx activity (C) and Grx1 protein expression (D), TrxR (E) and TXNIP (F) protein expression increased in NOS-3 overexpressing cells compared to cells transfected with the empty vector. Data are presented as mean±SEM (n=3 independent experiments) and the groups labeled with “a” were significantly statistical (p≤0.05) versus the corresponding control group. Representative Western blotting images are shown.
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f0015: High levels of nitric oxide induced activity and expression of redox proteins. Trx activity (A) and Trx1 protein expression (B), Grx activity (C) and Grx1 protein expression (D), TrxR (E) and TXNIP (F) protein expression increased in NOS-3 overexpressing cells compared to cells transfected with the empty vector. Data are presented as mean±SEM (n=3 independent experiments) and the groups labeled with “a” were significantly statistical (p≤0.05) versus the corresponding control group. Representative Western blotting images are shown.

Mentions: Proteins related to the thioredoxin and glutaredoxin systems are prominent players in thiol redox homeostasis in cells and were studied. Protein levels and activity of Trx1, Grx1 and levels of TrxR1 and TXNIP, increased significantly in NOS-3 overexpressing HepG2 cells (Fig. 3A–F). The simultaneous increase of both Trx1 and its opposing protein TXNIP is a conflicting situation likely a reflection of the cellular response to redox changes under the prevailing nitrosative conditions where Trx1 and TXNIP may not be interacting (see below).


Redox regulation of metabolic and signaling pathways by thioredoxin and glutaredoxin in NOS-3 overexpressing hepatoblastoma cells.

González R, López-Grueso MJ, Muntané J, Bárcena JA, Padilla CA - Redox Biol (2015)

High levels of nitric oxide induced activity and expression of redox proteins. Trx activity (A) and Trx1 protein expression (B), Grx activity (C) and Grx1 protein expression (D), TrxR (E) and TXNIP (F) protein expression increased in NOS-3 overexpressing cells compared to cells transfected with the empty vector. Data are presented as mean±SEM (n=3 independent experiments) and the groups labeled with “a” were significantly statistical (p≤0.05) versus the corresponding control group. Representative Western blotting images are shown.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528045&req=5

f0015: High levels of nitric oxide induced activity and expression of redox proteins. Trx activity (A) and Trx1 protein expression (B), Grx activity (C) and Grx1 protein expression (D), TrxR (E) and TXNIP (F) protein expression increased in NOS-3 overexpressing cells compared to cells transfected with the empty vector. Data are presented as mean±SEM (n=3 independent experiments) and the groups labeled with “a” were significantly statistical (p≤0.05) versus the corresponding control group. Representative Western blotting images are shown.
Mentions: Proteins related to the thioredoxin and glutaredoxin systems are prominent players in thiol redox homeostasis in cells and were studied. Protein levels and activity of Trx1, Grx1 and levels of TrxR1 and TXNIP, increased significantly in NOS-3 overexpressing HepG2 cells (Fig. 3A–F). The simultaneous increase of both Trx1 and its opposing protein TXNIP is a conflicting situation likely a reflection of the cellular response to redox changes under the prevailing nitrosative conditions where Trx1 and TXNIP may not be interacting (see below).

Bottom Line: The aim of this study was to ascertain whether Trx and/or Grx systems mediate the antiproliferative effect of NO on hepatoblastoma cells by modulating the redox-state of key proteins.Silencing of Trx1 and Grx1 neutralized the increases in CD95, Akt1 and pAkt levels induced by NO and produced a marked increase in caspase-3 and -8 activities in both control and NOS-3 overexpressing cells concomitant with a decrease in the number of cells.These results demonstrate that the antiproliferative effect of NO is actually hampered by Trx1 and Grx1 and support the strategy of weakening the thiolic antioxidant defenses when designing new antitumoral therapies.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain. Electronic address: raulangello@hotmail.com.

No MeSH data available.


Related in: MedlinePlus