The role of tocopherol cyclase in salt stress tolerance of rice (<Emphasis Type="Italic">Oryza sativa</Emphasis>)

Tocopherols synthesized exclusively by photosynthetic organisms are major antioxidants in biomembranes. In plants, tocopherol cyclase (TC/VTE1) catalyzes the conversion of 2,3-dimethyl-5-phytyl-1,4-benzoquinone (DMPBQ) to γ-tocopherol. In the present study, OsVTE1, which encodes a rice tocopherol cyclase ortholog, was cloned and characterized. OsVTE1 was induced significantly by abiotic stresses such as high salt, H₂O₂, drought, cold and by the plant hormones ABA and salicylic acid. The tissue-specific expression pattern and OsVTE1-promoter GUS activity assay showed that OsVTE1 was mainly expressed in the leaf, and also could be detected in the root, stem and panicle. Compared with control plants, transgenic plants with Os-VTE1 RNA interference (OsVTE1-RNAi) were more sensitive to salt stress whereas, in contrast, transgenic plants overexpressing OsVTE1 (OsVTE1-OX) showed higher tolerance to salt stress. The DAB in vivo staining showed that OsVTE1-OX plants accumulated less H₂O₂ than did control plants.     

The role of endoplasmic reticulum stress in emphysema results from cigarette smoke exposure

Apoptosis is of considerable importance in the pathogenesis of emphysema, and recent studies show that endoplasmic reticulum (ER) stress is involved in emphysema. In our research, we investigated the role of protein kinase RNA (PKR)-like ER kinase (PERK)/ eukaryotic initiation factor 2 alpha (eIF2α) pathway, the CCAAT enhancer-binding protein-homologous protein (CHOP) expression, caspase-12 activation and apoptosis in emphysema results from cigarette smoke (CS) exposure. Expression of phosphorylated-PERK (p-PERK), phospholated-eIF2α (p-eIF2α),CHOP and caspase-12 as well as the apoptosis rate are remarkably increased in rats after exposure to 2 months CS compared with control rats, significantly elevated in rats exposed to 4 months CS over rats exposed only to 2 months CS, and slightly decreased in ex-smoking rats in contrast to rats exposed to 4 months CS. Taken together, our results show that CS induces ER stress in lung epithelial cells, which may subsequently lead to lung injury in rats, and this might be a novel target for protection of pulmonary epithelial cells from ER stress injury in emphysema.     

NDP52 SUMOylation contributes to low-dose X-rays-induced cardiac hypertrophy through PINK1/Parkin-mediated mitophagy via MUL1/SUMO2 signalling

Radiation-induced heart damage caused by low-dose X-rays has a significant impact on tumour patients' prognosis, with cardiac hypertrophy being the most severe noncarcinogenic adverse effect. Our previous study demonstrated that mitophagy activation promoted cardiac hypertrophy, but the underlying mechanisms remained unclear. In the present study, PARL-IN-1 enhanced excessive hypertrophy of cardiomyocytes and exacerbated mitochondrial damage. Isobaric tags for relative and absolute quantification-based quantitative proteomics identified NDP52 as a crucial target mediating cardiac hypertrophy induced by low-dose X-rays. SUMOylation proteomics revealed that the SUMO E3 ligase MUL1 facilitated NDP52 SUMOylation through SUMO2. Co-IP coupled with LC–MS/MS identified a critical lysine residue at position 262 of NDP52 as the key site for SUMO2-mediated SUMOylation of NDP52. The point mutation plasmid NDP52^K262R inhibited mitophagy under MUL1 overexpression, as evidenced by inhibition of LC3 interaction with NDP52, PINK1 and LAMP2A. A mitochondrial dissociation study revealed that NDP52^K262R inhibited PINK1 targeting to endosomes early endosomal marker (EEA1), late/lysosome endosomal marker (LAMP2A) and recycling endosomal marker (RAB11), and laser confocal microscopy confirmed that NDP52^K262R impaired the recruitment of mitochondria to the autophagic pathway through EEA1/RAB11 and ATG3, ATG5, ATG16L1 and STX17, but did not affect mitochondrial delivery to lysosomes via LAMP2A for degradation. In conclusion, our findings suggest that MUL1-mediated SUMOylation of NDP52 plays a crucial role in regulating mitophagy in the context of low-dose X-ray-induced cardiac hypertrophy. Two hundred sixty-second lysine of NDP52 is identified as a key SUMOylation site for low-dose X-ray promoting mitophagy activation and cardiac hypertrophy. Collectively, this study provides novel implications for the development of therapeutic strategies aimed at preventing the progression of cardiac hypertrophy induced by low-dose X-rays.     

Acetylcholinesterase is associated with apoptosis in β cells and contributes to insulin-dependent diabetes mellitus pathogenesis

Acetylcholinesterase (AChE) expression is pivotal during apoptosis. Indeed, AChE inhibitors partially protect cells from apoptosis. Insulin-dependent diabetes mellitus (IDDM) is characterized in part by pancreatic β-cell apoptosis. Here, we investigated the role of AChE in the development of IDDM and analyzed protective effects of AChE inhibitors. Multiple low-dose streptozotocin (MLD-STZ) administration resulted in IDDM in a mouse model. Western blot analysis, cytochemical staining, and immunofluorescence staining were used to detect AChE expression in MIN6 cells, primary β cells, and apoptotic pancreatic β cells of MLD-STZ-treated mice. AChE inhibitors were administered intraperitoneally to the MLD-STZ mice for 30 days. Blood glucose, plasma insulin, and creatine levels were measured, and glucose tolerance tests were performed. The effects of AChE inhibitors on MIN6 cells were also evaluated. AChE expression was induced in the apoptotic MIN6 cells and primary β cells in vitro and pancreatic islets in vivo when treated with STZ. Induction and progressive accumulation of AChE in the pancreatic islets were associated with apoptotic β cells during IDDM development. The administration of AChE inhibitors effectively decreased hyperglycemia and incidence of diabetes, and restored plasma insulin levels and plasma creatine clearance in the MLD-STZ mice. AChE inhibitors partially protected MIN6 cells from the damage caused by STZ treatment. Induction and accumulation of AChE in pancreatic islets and the protective effects of AChE inhibitors on the onset and development of IDDM indicate a close relationship between AChE and IDDM.     

High-dose chemotherapy followed by autologous stem cell transplantation as a first-line therapy for high-risk primary breast cancer: a meta-analysis

Background and Objectives

Several trials have generated conflicting results about the results of high-dose chemotherapy followed by autologous stem cell transplantation (HDCT) for primary breast cancer. This meta-analysis summarizes the available evidence from all suitable studies.

Design and Methods

Prospective, randomized trials with HDCT as a first-line therapy for primary breast cancer were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival and overall survival); secondary endpoints included treatment-related mortality (TRM) and second (non-breast) cancers. We used a median age of 47, a PR positive rate of 50% and a premenopausal rate of 70% as cutoff values to complete the subgroup analyses, which were pre-planned according to the prepared protocol.

Results

Fourteen trials with 5747 patients were eligible for the meta-analysis. Compared with non-HDCT, non-significant second (non-breast) cancers (RR = 1.28; 95% CI = 0.82–1.98) and higher TRM (RR = 3.42; 95% CI = 1.32–8.86) were associated with HDCT for primary breast cancer. A significant DFS benefit of HDCT was documented (HR = 0.89; 95% CI = 0.79–0.99). No difference in OS (overall survival) was found when the studies were pooled (HR = 0.91; 95% CI = 0.82–1.00, p = 0.062). In subgroup analysis, age and hormone receptor status had a significant interaction with prolonged DFS and OS.

Conclusions

HDCT has a benefit on DFS and OS compared to SDC in some special patients with high-risk primary breast cancer.     

MC-12, an Annexin A1-Based Peptide, Is Effective in the Treatment of Experimental Colitis

Annexin A1 (ANXA1) inhibits NF-κB, a key regulator of inflammation, the common pathophysiological mechanism of inflammatory bowel diseases (IBD). MC-12, an ANXA1-based tripeptide, suppresses NF-κB activation. Here, we determined the efficacy of MC-12 in the control of IBD. Mice with colitis induced by dextran sodium sulfate (DSS) or 2,4,6-trinitro benzene sulfonic acid (TNBS) were treated with various doses of MC-12 administered intraperitoneally, orally or intrarectally. We determined colon length and the histological score of colitis, and assayed: in colon tissue the levels of TNF-α, IFN-γ, IL-1β, IL-6 and IL-10 by RT-PCR; prostaglandin E(2) (PGE(2)), cytoplasmic phospholipase A(2) (cPLA(2)) and myeloperoxidase by immunoassay; and COX-2 and NF- κB by immunohistochemistry; and in serum the levels of various cytokines by immunoassay. In both models MC-12: reversed dose-dependently colonic inflammation; inhibited by up to 47% myeloperoxidase activity; had a minimal effect on cytoplasmic phospholipase A(2); reduced significantly the induced levels of TNF-α, IFN-γ, IL-1β, IL-6 and IL-10, returning them to baseline. DSS and TNBS markedly activated NF-κB in colonic epithelial cells and MC-12 decreased this effect by 85.8% and 72.5%, respectively. MC-12 had a similar effect in cultured NCM460 normal colon epithelial cells. Finally, MC-12 suppressed the induction of COX-2 expression, the level of PGE(2) in the colon and PGE(2) metabolite in serum. In conclusion, MC-12, representing a novel class of short peptide inhibitors of NF-κB, has a strong effect against colitis in two preclinical models recapitulating features of human IBD. Its mechanism of action is complex and includes pronounced inhibition of NF-κB. MC-12 merits further development as an agent for the control of IBD.     

Maize Benefits the Predatory Beetle, Propylea japonica (Thunberg), to Provide Potential to Enhance Biological Control for Aphids in Cotton

Background

Biological control provided by natural enemies play an important role in integrated pest management. Generalist insect predators provide an important biological service in the regulation of agricultural insect pests. Our goal is to understand the explicit process of oviposition preference, habitat selection and feeding behavior of predators in farmland ecosystem consisting of multiple crops, which is central to devising and delivering an integrated pest management program.

Methodology

The hypotheses was that maize can serve as habitat for natural enemies and benefits predators to provide potential to enhance biological control for pest insects in cotton. This explicit process of a predatory beetle, Propylea japonica, in agricultural ecosystem composed of cotton and maize were examined by field investigation and stable carbon isotope analysis during 2008–2010.

Principal Finding

Field investigation showed that P. japonica adults will search host plants for high prey abundance before laying eggs, indicating indirectly that P. japonica adults prefer to inhabit maize plants and travel to cotton plants to actively prey on aphids. The δ¹³C values of adult P. japonica in a dietary shift experiment found that individual beetles were shifting from a C₃- to a C₄-based diet of aphids reared on maize or cotton, respectively, and began to reflect the isotope ratio of their new C₄ resources within one week. Approximately 80–100% of the diet of P. japonica adults in maize originated from a C₃-based resource in June, July and August, while approximately 80% of the diet originated from a C₄-based resource in September.

Conclusion/Significance

Results suggest that maize can serve as a habitat or refuge source for the predatory beetle, P. japonica, and benefits predators to provide potential to enhance biological control for insect pests in cotton.     

Nix Protein Positively Regulates NF-��B Activation in Gliomas

Previous reports indicate that the NIX/BNIP3L gene acts as a pro-apoptotic factor by interacting with BCL2 and BCL-XL, playing an important role in hypoxia-dependent cell death and acting as a tumor suppressor. However, many studies also showed that NIX is linked to a protective role and cell survival in cancer cells. Nuclear factor-κB (NF-κB) can attenuate apoptosis in human cancers in response to chemotherapeutic agents and ionizing radiation. We observed an absence of i-κBα (NF-κB activation inhibitor) expression, but a greater expression of Nix and p-NF-κB proteins in the Nix-wt U251 cells, which was not observed in the Nix-kn cells under hypoxic conditions. Using electrophoretic mobility shift assay (EMSA) and luciferase detection, the activation of NF-κB was detected only in the Nix-wt U251 cells with hypoxia. These data imply that Nix protein might play a role in the positive regulation of the NF-κB pathway. Moreover, 46 cases of glioma also showed high levels of Nix protein expression, which was always accompanied by high p-NF-κB expression. Patients with Nix (+) showed less tissue apoptosis behavior in glioblastoma (GBM), unlike that observed in the Nix-negative patients (−). The same apoptotic tendency was also identified in anaplastic astrocytoma (AA) groups, but not in astrocytoma (AS). On analyzing the Kaplan-Meier curve, better tumor-free survival was observed only in cases of astrocytoma, and not in AA and GBM. Thus, our study indicates that Nix protein might have multiple functions in regulating glioma behaviors. In the low-grade gliomas (astrocytoma) with low expression of NF-κB, the cell death-inducing function that occurs through a Bax mechanism might predominate and act as a tumor suppressor. While in the malignant gliomas (AA and GBM), with higher expression of the NIX gene and with activity of the NF-κB pathway, the oncogene function of Nix was predominant.