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Abstract: Reactive oxygen species (ROS) were generated in all oxygen-utilizing organisms. Peroxiredoxin II (Prx II) as one of antioxidant enzymes may play a protective role against the oxidative damage caused by ROS. In order to define the role of Prx II in organismal aging, we evaluated cellular senescence in Prx II−/− mouse embryonic fibroblast (MEF). As compared to wild type MEF, cellular senescence was accelerated in Prx II−/− MEF. Senescence-associated (SA)-β-galactosidase (Gal)-positive cell formation was about 30% higher in Prx II−/− MEF. N-Acetyl-l-cysteine (NAC) treatment attenuated SA-β-Gal-positive cell formation. Prx II−/− MEF exhibited the higher G2/M (41%) and lower S (1.6%) phase cells as compared to 24% and 7.4% in wild type MEF, respectively. A high increase in the p16 and a slight increase in the p21 and p53 levels were detected in PrxII−/− MEF cells. The cellular senescence of Prx II−/− MEF was correlated with the organismal aging of Prx II−/− mouse skin. While extracellular signal-regulated kinase (ERK) and p38 activation was detected in Prx II−/− MEF, ERK and c-Jun N-terminal kinase (JNK) activation was detected in Prx II−/− skin. These results suggest that Prx II may function as an enzymatic antioxidant to prevent cellular senescence and skin aging. [Copyright &y& Elsevier]

Abstract: Thymosin beta-4 (TB4) is an actin-sequestering protein to control cytoskeletal reorganization. Here, we investigated whether TB4 proteins (TB4P) affect tumor microenvironment by measuring hypoxia-inducible transcription factor (HIF)-1α stabilization in cervical tumor cells, since TB4P reduced paclitaxel-induced cell death rate. TB4P increased HIF-1α stabilization and transactivation, which is measured by the increase of hypoxia response element (HRE)-luciferase activity and target gene, vascular endothelial growth factor (VEGF) transcription. TB4P also elevated ERK phosphorylation. PD98059, ERK inhibitor reduced HIF-1α increased by TB4P. Paclitaxel-induced cell death was inhibited by hypoxia conditioning that increased HIF-1α stabilization and ERK phosphorylation. PD98059 reversed paclitaxel-induced cell death which was attenuated by hypoxia. Collectively, TB4P could lead tumor cell microenvironment to hypoxia condition, which might be resulted in antitumor drug-resistance induction. It suggests that soluble TB4P could be a novel target to control tumor cell death by regulating tumor cell microenvironment. [Copyright &y& Elsevier]