Glucose alleviates cadmium toxicity by increasing cadmium fi xation in root cell wall and sequestration into vacuole in Arabidopsis

Glucose (Glu) is involved in not only plant physiological and developmental events but also plant responses to abiotic stresses. Here, we found that the exogenous Glu improved root and shoot growth, reduced shoot cadmium (Cd) concentration, and rescued Cd-induced chlorosis in Arabidopsis thaliana (Columbia ecotype, Col-0) under Cd stressed conditions. Glucose increased Cd retained in the roots, thus reducing its translocation from root to shoot significantly. The most Cd retained in the roots was found in the hemicellulose 1. Glucose combined with Cd (Glu t Cd) treatment did not affect the content of pectin and its binding capacity of Cd while it increased the content of hemicelluloses 1 and the amount of Cd retained in it significantly. Furthermore, Leadmium Green staining indicated that more Cd was compartmented into vacuoles in Glu t Cd treatment compared with Cd treatment alone, which was in accordance with the significant upregulation of the expression of tonoplast-localized metal transporter genes, suggesting that com-partmentation of Cd into vacuoles also contributes to the Glu-alleviated Cd toxicity. Taken together, we demonstrated that Glu-alleviated Cd toxicity is mediated through increas-ing Cd fixation in the root cell wall and sequestration into the vacuoles.

An eukaryotic translation initiation factor, AteIF_5A-2,affects cadmium accumulation and sensitivity in Arabidopsis

Cadmium (Cd) is one of the most toxic elements and can be accumulated in plants easily; meanwhile, eIF5A is a highly conserved protein in all eukaryotic organisms. The present work tried to investigate whether eIF5A is involved in Cd accumulation and sensitivity in Arabidopsis (Arabidopsis thaliana L.) by comparing the wild-type Columbia-0 (Col-0) with a knockdown mutant of AteIF5A-2, fbr12-3 under Cd stress conditions. The results showed that the mutant fbr12-3 accumulated more Cd in roots and shoots and had significantly lower chlorophyll content, shorter root length, and smaller biomass, suggesting that downregulation of AteIF5A-2 makes the mutant more Cd sensitive. Real-time polymerase chain reaction revealed that the expressions of metal transporters involved in Cd uptake and translocation including IRT1, ZIP1, AtNramp3, and AtHMA4 were significantly increased but the expressions of PCS1 and PCS2 related to Cd detoxification were decreased notably in fbr12-3 compared with Col-0. As a result, an increase in MDA and H2O2 content but decrease in root trolox, glutathione and proline content under Cd stress was observed, indicating that a severer oxidative stress occurs in the mutant. All these results demonstrated for the first time that AteIF5A influences Cd sensitivity by affecting Cd uptake, accumulation, and detoxification in Arabidopsis.

Targeted inhibition of myeloid-derived suppressor cells in the tumor microenvironment by low-dose doxorubicin to improve immune efficacy in murine neuroblastoma

Background:High agglomeration of myeloid-derived suppressor cells(MDSCs)in neuroblastoma(NB)impeded therapeutic effects.This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin(DOX)to enhance immune efficacy in NB.Methods:Bagg albino(BALB/c)mice were used as tumor-bearing mouse models by injecting Neuro-2a cells,and MDSCs were eliminated by DOX or dopamine(DA)administration.Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX,5.0 mg/kg DOX,50.0 mg/kg DA,and control groups(n=20).The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition.NB antigen-specific cytotoxic T cells(CTLs)were prepared.Tumor-bearing mice were randomly divided into DOX,CTL,anti-ganglioside(GD2),DOX+CTL,DOX+anti-GD2,and control groups.Following low-dose DOX administration,immunotherapy was applied.The levels of human leukocyte antigen(HLA)-I,CD8,interleukin(IL)-2 and interferon(IFN)-γin peripheral blood,CTLs,T-helper 1(Th1)/Th2 cytokines,perforin,granzyme and tumor growth were compared among the groups.The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results.Results:The slowest tumor growth(F=6.095,P=0.018)and strongest MDSC inhibition(F=14.632,P=0.001)were observed in 2.5 mg/kg DOX group.Proliferation of T cells was increased(F=448.721,P<0.001)and then decreased(F=2.047,P=0.186).After low-dose DOX administration,HLA-I(F=222.489),CD8(F=271.686),Th1/Th2 cytokines,CD4^(+)and CD8^(+)lymphocytes,granzyme(F=2376.475)and perforin(F=488.531)in tumor,IL-2(F=62.951)and IFN-γ(F=240.709)in peripheral blood of each immunotherapy group were all higher compared with the control group(all ofP values<0.05).The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups.Conclusions:Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression,thereby fostering immune efficacy in NB.