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Antagonizing TNF-α signaling attenuates chronic inflammatory disease, but is associated with adverse effects on the cardiovascular system. Therefore the impact of TNF-α on basal control of redox signaling events needs to be understand in more depth. This is particularly important for the Keap1/Nrf2 pathway in the heart and in the present study we hypothesized that inhibition of a low level of TNF-α signaling attenuates the TNF-α dependent activation of this cytoprotective pathway. HL-1 cardiomyocytes and TNF receptor1/2 (TNFR1/2) double knockout mice (DKO) were used as experimental models. TNF-α (2–5 ng/ml, for 2 h) evoked significant nuclear translocation of Nrf2 with increased DNA/promoter binding and transactivation of Nrf2 targets. Additionally, this was associated with a 1.5 fold increase in intracellular glutathione (GSH). Higher concentrations of TNF-α (>10–50 ng/ml) were markedly suppressive of the Keap1/Nrf2 response and associated with cardiomyocyte death marked by an increase in cleavage of caspase-3 and PARP. In vivo experiments with TNFR1/2-DKO demonstrates that the expression of Nrf2-regulated proteins (NQO1, HO-1, G6PD) were significantly downregulated in hearts of the DKO when compared to WT mice indicating a weakened antioxidant system under basal conditions. Overall, these results indicate that TNF-α exposure has a bimodal effect on the Keap1/Nrf2 system and while an intense inflammatory activation suppresses expression of antioxidant proteins a low level appears to be protective.

The differences of PBDE absorption, accumulation, and metabolism in different cultivars of the same crop are rarely explored. This study used 14 C tracing to fully demonstrate the uptake and transformation of soil-borne BDE209 in three rice cultivars, including two indica (HHZ and YD1) and one japonica cultivars (NJ3). Results showed that about 6.9, 17.2, and 17.4% of the applied 14 C-BDE209 were transformed to 14 C-metabolites in soils planted with HHZ, YD1, and NJ3, respectively. The 14 C-BDE209 and its 14 C-metabolites in soil could be absorbed by the rice and gradually transported to its root, stem, leaf, and grain, with the total whole-plant uptake of 8.52, 4.55 and 3.43 nmol for HHZ, YD1, and NJ3, respectively. The cultivar of HHZ had the greatest whole-plant 14 C absorption but the lowest ΣPBDEs residues in its grain, with the ΣPBDEs of 421.8, 454.2 and 967.0 ng g -1 for HHZ, YD1, and NJ3, respectively. BDE-209 accounted for 90%, 31% and 50% of the ΣPBDEs in the grain from HHZ, YD1, and NJ3, respectively. The estimated daily intake (EDI) amounts of ΣPBDEs were 928, 1056, and 2675 ng kg -1  bw d -1 via consuming rice grains from HHZ, YD1, and NJ3, respectively, which were below the safe threshold limits for human consumption. This study proved the different BDE-209 absorption, accumulation and transformation in different rice cultivars, which potentially suggests the need of considering cultivar differences in assessing the dietary risks of PBDEs., (Copyright © 2019 Elsevier B.V. All rights reserved.)