Upon exposure to various environmental stresses such as arsenite, hypoxia, and heat shock, cells inhibit their translation and apoptosis and then repair stress-induced alterations, such as DNA damage and the accumulation of misfolded proteins. These types of stresses induce the formation of cytoplasmic RNA granules called stress granules (SGs). SGs are storage sites for the many mRNAs released from disassembled polysomes under these stress conditions and are essential for the selective translation of stress-inducible genes. Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer. In this study, we examined the role of G3BP2, a close relative of G3BP1, in SG formation. Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. G3BP2 formed a homo-multimer and a hetero-multimer with G3BP1. Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli. Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses.

Cells can undergo two alternative fates following exposure to environmental stress: they either induce apoptosis or inhibit apoptosis and then repair the stress-induced alterations. These processes minimize cell loss and prevent the survival of cells with aberrant DNA and protein alterations. These two alternative fates are partly controlled by stress granules (SGs). While arsenite, hypoxia, and heat shock induce the formation of SGs that inhibit apoptosis, X-ray irradiation and genotoxic drugs do not induce SGs, and they are more prone to trigger apoptosis. However, it is unclear precisely how SGs control apoptosis. This study found that SGs suppress the elevation of reactive oxygen species (ROS), and this suppression is essential for inhibiting ROS-dependent apoptosis. This antioxidant activity of SGs is controlled by two SG components, GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and ubiquitin-specific protease 10 (USP10). G3BP1 elevates the steady-state ROS level by inhibiting the antioxidant activity of USP10. However, following exposure to arsenite, G3BP1 and USP10 induce the formation of SGs, which uncovers the antioxidant activity of USP10. We also found that the antioxidant activity of USP10 requires the protein kinase activity of ataxia telangiectasia mutated (ATM). This work reveals that SGs are critical redox regulators that control cell fate under stress conditions.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and the viral oncoprotein Tax plays key roles in the immortalization of human T cells, lifelong persistent infection, and leukemogenesis. We herein identify the ubiquitin-specific protease 10 (USP10) as a Tax-interactor in HTLV-1-infected T cells. USP10 is an antistress factor against various environmental stresses, including viral infections and oxidative stress. On exposure to arsenic, an oxidative stress inducer, USP10 is recruited into stress granules (SGs), and USP10-containing SGs reduce reactive oxygen species (ROS) production and inhibit ROS-dependent apoptosis. We found that interaction of Tax with USP10 inhibits arsenic-induced SG formation, stimulates ROS production, and augments ROS-dependent apoptosis in HTLV-1-infected T cells. These findings suggest that USP10 is a host factor that inhibits stress-induced ROS production and apoptosis in HTLV-1-infected T cells; however, its activities are attenuated by Tax. A clinical study showed that combination therapy containing arsenic is effective against some forms of ATL. Therefore, these findings may be relevant to chemotherapy against ATL.

In 1985, 362 primary schoolchildren and their 319 mothers were surveyed in Hong Kong to study the possible relationship of air pollution to respiratory illnesses. Using nitrogen dioxide (NO2) measured by personal samplers as a measure of air pollution, the study aimed to identify the major sources of NO2 in the indoor environment and see whether its increased presence was associated with respiratory symptoms. The levels of NO2 among the mothers was found to increase by 21% if dust exposure was reported from the workplace, 18% if they used such cooking fuels as liquid petroleum gas or kerosene, 11% when kitchens did not have ventilating fans, and 10% when incense was burned at home. In terms of respiratory symptoms, an increase in NO2 levels of 19% was reported among those with allergic rhinitis and 18% among those with chronic cough. The levels of NO2 among children were correlated with levels measured in classrooms, all of which had opened windows so that the NO2 came from outdoors. No association was found between children's NO2 levels and respiratory symptoms. With the exception of smoking by the father and the children's NO2 levels, no association was found between smoking at home and NO2 levels.

Controlled Trial of Worksite Health Education Through Face-to-Face Counseling vs. Email on Drinking Behavior Modification: Ikuno ARAKI, et al. Department of Medicine & OccupationalHealth, ExxonMobil Yugen Kaisha-This study examined the effectiveness of a traditional face-to-face health education and e-mail health education on alcohol usage among male workers in comparison with a control group. Male workers at a manufacturing plant (N=36) who had abnormal serum γ-GTP were stratified by age and job types, then randomized into three groups: face-to-face education, e-mail education, and the control. The subjects were assessed on their knowledge about and attitude towards drinking, reported alcohol consumption, and serum γ-GTP before the start of education and 2 months later after comparison of the education. Paired t-test and repeated ANOVA were conducted to test the significance of changes pre and post the intervention and across groups. In the face-to-face group, knowledge (p=0.001), attitude (p=0.026), alcohol consumption (p=0.003) and serum γ-GTP showed significant improvement. In the e-mail group, only alcohol consumption showed marginal improvement (p=0.077). In the control group, no variables remarkably changed. These results indicate that the face-to-face health education was more effective than the e-mail program. We discuss why the face-to-face approach was superior to the e-mail approach in this study by referring to self-monitoring, goal setting processes and timely feedback. We concluded that further studies are warranted to identify the effect of health education using e-mails and other network tools in consideration of the above three factors. (J Occup Health 2006; 48: 239-245)