The antiallergic activity of Polygoni cuspidati radix (PR) and the mechanism of action by which it functions were investigated in this study. The extract of PR exhibited potent inhibitory activity in mast cells; its IC50 values were 62 +/- 2.1 microg/ml for RBL-2H3 mast cells and 46 +/- 3.2 microg/m for bone marrow-derived mast cells by antigen stimulation, and it also suppressed the expression of tumor necrosis factor-alpha and interleukin-4 in RBL-2H3 cells. According to the in vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis, in a dose-dependent manner. With regard to its mechanism of action, PR inhibited the activating phosphorylation of Syk, a key signaling protein for the activation of mast cells. It also suppressed Akt and the mitogen-activated protein kinases ERK1/2, p38, and JNK, which are critical for the production of various inflammatory cytokines in mast cells. The results of the study indicate that the antiallergic activity of PR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk activating phosphorylation in mast cells. 相似文献
Aroma serves as one of the decisive factors influencing the value of banana commodities. Most of characteristic volatile organic components (VOCs) are formed during post-harvesting. However, the changing of VOCs of banana at different post-harvesting stages remain ambiguous. In this study, the VOCs of Cavendish banana for the four typical post-harvesting stages (green stage/half of yellow stage/yellow ripening stage/over ripening stage) are clarified using headspace solid phase micro-extraction (HS-SPME), combined with gas chromatography-mass spectrometry (GC–MS). The results inferred that the relative content of branched-chain esters such as acetate and butyrate, which form the main contributors of aroma in bananas, is higher in the T2 and T3 stages. Further, RNA-Seq technology was employed to clarify the formation mechanism of banana aroma in the post-harvesting stage. The MaTGL4 gene of the linoleic acid metabolism pathway and the MaBCAT3 and MaBCAT5 genes of the valine, leucine and isoleucine degradation pathway in banana suggest the expression is active late in the ripening stage, and the upregulated expression of these genes is analogous to the formation of aroma components such as branched-chain esters and hexenal. The above results not only provide baseline data on the differences in physical and chemical properties of VOCs in various post-harvesting stages of banana production, but also provide theoretical guidance facilitating the subsequent improvement of the commercial value of bananas through genetic improvement.
Obstructions to replication fork progression, referred to collectively as DNA replication stress, challenge genome stability. In Saccharomyces cerevisiae, cells lacking RTT107 or SLX4 show genome instability and sensitivity to DNA replication stress and are defective in the completion of DNA replication during recovery from replication stress. We demonstrate that Slx4 is recruited to chromatin behind stressed replication forks, in a region that is spatially distinct from that occupied by the replication machinery. Slx4 complex formation is nucleated by Mec1 phosphorylation of histone H2A, which is recognized by the constitutive Slx4 binding partner Rtt107. Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1. We propose that Slx4 complexes promote robust checkpoint signaling by Mec1 by stably recruiting Dpb11 within a discrete domain behind the replication fork, during DNA replication stress. 相似文献
Although p53 is frequently mutated in human cancers, about 80% of human melanomas retain wild-type p53. Here we report that PHGDH, the key metabolic enzyme that catalyzes the rate-limiting step of the serine biosynthesis pathway, is a target of p53 in human melanoma cells. p53 suppresses PHGDH expression and inhibits de novo serine biosynthesis. Notably, upon serine starvation, p53-mediated cell death is enhanced dramatically in response to Nutlin-3 treatment. Moreover, PHGDH has been found recently to be amplified frequently in human melanomas. We found that PHGDH overexpression significantly suppresses the apoptotic response, whereas RNAi-mediated knockdown of endogenous PHGDH promotes apoptosis under the same treatment. These results demonstrate an important role of p53 in regulating the serine biosynthesis pathway through suppressing PHGDH expression and reveal serine deprivation as a novel approach to sensitize p53-mediated apoptotic responses in human melanoma cells. 相似文献