Title:Implication of Thioredoxin 1 and Glutaredoxin 1 in H2O2-induced
Phosphorylation of JNK and p38 MAP Kinases
Volume: 25
Issue: 3
Author(s): Efthymios Poulios*, Vasiliki Roupaka, Constantinos Giaginis, Dimitrios Galaris and Giannis Spyrou*
Affiliation:
- Department of Food Science and Nutrition, School of the Environment, University of the Aegean, Metropolite
Ioakeim 2, 81400 Myrina, Lemnos, Greece
- Department of Biomedical and Clinical
Sciences, Division of Clinical Chemistry, Medical Faculty, S-581 85 Linköping, Sweden
Keywords:
Thioredoxin, Glutaredoxin, JNK, Hydrogen peroxide, Redox signaling, MAPKs.
Abstract:
Background. Aerobic organisms continuously generate small amounts of
Reactive Oxygen Species (ROS), which are involved in the oxidation of sensitive
cysteine residues in proteins, leading to the formation of disulfide bonds. Thioredoxin
(Trx1) and Glutaredoxin (Grx1) represent key antioxidant enzymes reducing disulfide
bonds.
Objective. In this work, we have focused on the possible protective effect of Trx1 and
Grx1 against oxidative stress-induced DNA damage and apoptosis-signaling, by
studying the phosphorylation of MAP kinases.
Methods. Trx1 and Grx1 were overexpressed or silenced in cultured H1299 non-small
cell lung cancer epithelial cells. We examined cell growth, DNA damage, and the
phosphorylation status of MAP kinases following treatment with H2O2.
Results. Overexpression of both Trx1 and Grx1 had a significant impact on the growth
of H1299 cells and provided protection against H2O2-induced toxicity, as well as acute
DNA single-strand breaks. Conversely, silencing of these proteins exacerbated DNA
damage. Furthermore, overexpression of Trx1 and Grx1 inhibited the rapid
phosphorylation of JNK (especially at 360 min of treatment, ****p=0.004 and
**p=0.0033 respectively) and p38 MAP kinases (especially at 360 min of treatment,
****p<0.0001 and ***p=0.0008 respectively) during H2O2 exposure, while their silencing
had the opposite effect (especially at 360 min of treatment, ****p<0.0001).
Conclusion. These results suggest that both Trx1 and Grx1 have protective roles
against H2O2 induced toxicity, emphasizing their significance in mitigating oxidative
stress-related cellular damage.