Changes in antioxidant system and sucrose metabolism in maize varieties exposed to Cd.

Different maize varieties respond differentially to cadmium (Cd) stress. However, the physiological mechanisms that determine the response are not well defined. Antioxidant systems and sucrose metabolism help plants to cope with abiotic stresses, including Cd stress. The relationship of these two systems in the response to Cd stress is unclear. Seed is sensitive to Cd stress during germination. In this study, we investigated changes in the antioxidant system, sucrose metabolism, and abscisic acid and gibberellin concentrations in two maize varieties with low (FY9) or high (SY33) sensitivities to Cd under exposure to CdCl2 (20 mg L-1) at different stages of germination (3, 6, and 9 days).The seed germination and seedling growth were inhibited under Cd stress. The superoxide, malondialdehyde, and proline concentrations, and the superoxide dismutase, peroxidase, catalase, and lipoxygenase activities increased compared with those of the control (CK; without Cd). The expression levels of three genes (ZmOPR2, ZmOPR5, and ZmPP2C6) responsive to oxidative stress increased differentially in the two varieties under Cd stress. The activity of the antioxidant system and the transcript levels of oxidative stress-responsive genes were higher in the Cd-tolerant variety, FY9, than in the sensitive variety, SY33. Sucrose metabolism was increased under Cd stress compared with that of the CK and was more active in the Cd-sensitive variety, SY33. These results suggest that the antioxidant system is the first response to Cd stress in maize, and that sucrose metabolism is cooperative and complementary under exposure to Cd.

Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth.

The importance of BET protein BRD4 in gene transcription is well recognized through the study of chemical modulation of its characteristic tandem bromodomain (BrD) binding to lysine-acetylated histones and transcription factors. However, while monovalent inhibition of BRD4 by BET BrD inhibitors such as JQ1 blocks growth of hematopoietic cancers, it is much less effective generally in solid tumors. Here, we report a thienodiazepine-based bivalent BrD inhibitor, MS645, that affords spatially constrained tandem BrD inhibition and consequently sustained repression of BRD4 transcriptional activity in blocking proliferation of solid-tumor cells including a panel of triple-negative breast cancer (TNBC) cells. MS645 blocks BRD4 binding to transcription enhancer/mediator proteins MED1 and YY1 with potency superior to monovalent BET inhibitors, resulting in down-regulation of proinflammatory cytokines and genes for cell-cycle control and DNA damage repair that are largely unaffected by monovalent BrD inhibition. Our study suggests a therapeutic strategy to maximally control BRD4 activity for rapid growth of solid-tumor TNBC cells.