The persistence of leukemia stem cells (LSCs) is one of the leading causes of chemoresistance in acute myeloid leukemia (AML). To explore the factors important in LSC-mediated resistance, we use mass spectrometry to screen the factors related to LSC chemoresistance and defined IFN-γ-inducible lysosomal thiol reductase (GILT) as a candidate. We found that the GILT expression was upregulated in chemoresistant CD34+ AML cells. Loss of function studies demonstrated that silencing of GILT in AML cells sensitized them to Ara-C treatment both in vitro and in vivo. Further mechanistic findings revealed that the ROS-mediated mitochondrial damage plays a pivotal role in inducing apoptosis of GILT-inhibited AML cells after Ara-C treatment. The inactivation of PI3K/Akt/ nuclear factor erythroid 2-related factor 2 (NRF2) pathway, causing reduced generation of antioxidants such as SOD2 and leading to a shifted ratio of GSH/GSSG to the oxidized form, contributed to the over-physiological oxidative status in the absence of GILT. The prognostic value of GILT was also validated in AML patients. Taken together, our work demonstrated that the inhibition of GILT increases AML chemo-sensitivity through elevating ROS level and induce oxidative mitochondrial damage-mediated apoptosis, and inhibition of the PI3K/Akt/NRF2 pathway enhances the intracellular oxidative state by disrupting redox homeostasis, providing a potentially effective way to overcome chemoresistance of AML. 相似文献
Abstract: Using the fluorescent differential display technique, we analysed the differential expression of genes related to Bombyx mori nuclear polyhedrosis virus (BmNPV) resistance. Silkworm strains studied included the highly resistant strain NB, highly susceptible strain 306 and near-isogenic line 306NNZZ. One novel gene was identified and named Bmsop2 for its high similarity with the Sop2 protein of other species. It was identified to be linked to BmNPV susceptibility by Northern blotting and real-time polymerase chain reaction. The results indicated that it was actively expressed in midguts of strains 306, NB and the eighth generation of backcross (BC8) of strain 306NNZZ which had been treated with BmNPV. But the expression level was low in the midguts of the control. In the mean time, the expression of Bmsop2 was the highest in strain 306 treated with BmNPV while it was the lowest in strain 306 not treated with BmNPV. Our study showed that Bmsop2 is a differentially expressed gene in strains NB, 306 and 306NNZZ which have different levels of resistance to BmNPV. 相似文献
Sweetness is one of the key factors determining peach fruit quality. To better understand the molecular basis of gibberellic acid (GA) and 1-naphthaleneacetic acid (NAA) interference with sugar biosynthesis, a middle-late maturing commercial cultivar, ‘Jinxiu’ yellow peach fruit, was treated with three different concentrations of GA4+7 and four of NAA. Fruit weight, firmness, total soluble solids, different sugar contents and the expression level of sugar-related genes were evaluated. The results showed that maximum increase in cv. ‘Jinxiu’ peach fruit size and sucrose content was with 1.25 mM GA4+7, compared to control fruits and the other treatments during the ripening stages. The sucrose-phosphate synthase gene (PpSPS2) which had a high level of expression and positive correlation with sucrose content was significantly regulated by 1.25 mM GA4+7 in the final ripening stages. 0.5 mM NAA treatments significantly reduced the sucrose content and fruit size. Ninety percent of the fruits were deformed or dropped from the trees with treatments of 1 mM NAA and 2 mM NAA in the early development period. The crosstalk of different phytohormones and the related genes will be further investigated to get an insight into the inherent association between hormone control and sugar accumulation.
Although caspases have been demonstrated to be involved in artemisinin (ARTE)-induced apoptosis, their exact functions are
not well understood. The aim of this report is to explore the roles of caspase-8, -9 and -3 during ARTE-induced apoptosis
in human lung adenocarcinoma (ASTC-a-1) cells. ARTE treatment induces a rapid generation of reactive oxygen species (ROS),
and ROS-dependent apoptosis as well as the activation of caspase-8, -9 and -3 via time- and dose-dependent fashion. Of upmost
importance, inhibition of caspase-8 or -9, but not caspase-3, almost completely blocks the ARTE-induced not only activation
of the caspase-8, -9 and -3 but also apoptosis. In addition, the apoptotic process triggered by ARTE does not involve the
Bid cleavage, tBid translocation, significant loss of mitochondrial membrane potential and cytochrome c release from mitochondria.
Moreover, silencing Bax/Bak does not prevent the ATRE-induced cell death as well as the activation of caspase-8, -9 and -3.
Collectively, our data firstly demonstrate that ARTE triggers a ROS-mediated positive feedback amplification activation loop
between caspase-8 and -9 independent of mitochondria, which dominantly mediated the ARTE-induced apoptosis via a caspase-3-independent
apoptotic pathway in ASTC-a-1 cells. Our findings imply a potential to develop new derivatives from artemisinin to effectively
initiate the amplification activation loop of caspases. 相似文献
Light use efficiency (LUE) is an important variable in carbon cycle and climate change research. We present an investigation of remotely estimating midday LUE using the green chlorophyll index (CIgreen) derived from the cloud-free Moderate Resolution Imaging Spectroradiometer (MODIS) images in maize, coniferous forest and grassland. Similar temporal patterns are observed in both canopy chlorophyll content and midday LUE which indicates that the chlorophyll content in the maize canopy servers as a proxy of midday LUE (R2 = 0.736, p < 0.001). Therefore, the CIgreen, tested as a good indicator of canopy chlorophyll content (R2 = 0.840, p < 0.001), has been demonstrated to be a reliable candidate in providing reasonable estimates of midday LUE with determination coefficient R2 equals to 0.820 and a root mean square error (RMSE) of 0.002 mol CO2 per mol incident photosynthetic photon flux density (PPFD). Further validation of the prediction model derived from the maize site demonstrates that the CIgreen has potential to be applied in the coniferous forest and grassland ecosystems with RMSE of 0.005 and 0.004 mol CO2 mol−1 PPFD, respectively. A comparison analysis between different vegetation types is included and these results could be helpful in the development of future LUE and terrestrial models. 相似文献