Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity

It is widely accepted that reactive oxygen species (ROS) promote tumorigenesis. However, the exact mechanisms are still unclear. As mice lacking the peroxidase peroxiredoxin1 (Prdx1) produce more cellular ROS and die prematurely of cancer, they offer an ideal model system to study ROS‐induced tumorigenesis. Prdx1 ablation increased the susceptibility to Ras‐induced breast cancer. We, therefore, investigated the role of Prdx1 in regulating oncogenic Ras effector pathways. We found Akt hyperactive in fibroblasts and mammary epithelial cells lacking Prdx1. Investigating the nature of such elevated Akt activation established a novel role for Prdx1 as a safeguard for the lipid phosphatase activity of PTEN, which is essential for its tumour suppressive function. We found binding of the peroxidase Prdx1 to PTEN essential for protecting PTEN from oxidation‐induced inactivation. Along those lines, Prdx1 tumour suppression of Ras‐ or ErbB‐2‐induced transformation was mediated mainly via PTEN.     

Critical threshold meal size and molt initiation in Rhodnius prolixus

The molting process and body growth in Rhodnius prolixus (Hemiptera: Reduviidae) (Ståhl, 1859) are significantly influenced by the availability and quality of food. Based on the body weight of each stage, the present study provides estimates of a potential critical weight threshold required for molt initiation in R. prolixus. In addition, a new measure given by the area under the weight curve is proposed, which encapsulates both body weight and time. It is shown that this measure is consistent with the data, and allows the estimation of a pre‐refractory period (i.e. the time interval between the moment at which the critical weight threshold is reached and the moment when no further meals are accepted). The present analysis estimates the critical weight threshold as 1.6, 5.3, 12.9, 42.0 and 97.0 mg for stages 1–5, respectively, whereas the values of the area under the curve threshold as 5, 16, 31.2, 159.7 and 329.9 mg days for stages 1–5, respectively. The results of the present study confirm the existence of a weight‐dependent mechanism for the initiation of molting in R. prolixus.     

温度对米象成虫飞行行为的影响

为探明温度对米象成虫的飞行行为的影响,应用起飞测定装置和昆虫飞行磨对不同温度条件下米象成虫的飞行参数进行了测定。结果显示23℃时,米象即可起飞;23～35℃内,60.0%～73.3%的米象个体具备飞行能力;温度对米象雌成虫的24 h累计飞行距离、24 h累计飞行时间和飞行速度均有显著影响,随温度的升高其飞行能力先增强后减弱,在32℃时上述3个飞行参数均有最大值。米象雄成虫的24 h累计飞行距离、24 h累计飞行时间和飞行速度受温度影响不显著,整体随测定温度的增加呈现先增大后减小的趋势,在29℃时有最大值。米象雌雄成虫的日常日行活动呈现一定的节律性,每日上午和傍晚以后有两个飞行活动高峰。研究结果明确了米象成虫在不同温度条件下的飞行行为特征,可为米象的扩散和害虫感染的预防提供数据支持。     

Roles of Eukaryotic Initiation Factor 5A2 in Human Cancer

Eukaryotic initiation factor 5A (eIF5A), the only known cellular protein containing the amino acid hypusine, is an essential component of translation elongation. eIF5A2, one of the two isoforms in the eIF5A family, is reported to be a novel oncogenic protein in many types of human cancer. Both in vitro and in vivo studies showed that eIF5A2 could initiate tumor formation, enhance cancer cell growth, and increase cancer cell motility and metastasis by inducing epithelial-mesenchymal transition. Accumulatied evidence suggests that eIF5A2 is a useful biomarker in the prediction of cancer prognoses and serves as an anticancer molecular target. In this review, we will focus on updating current knowledge of the EIF5A2 gene in human cancers. The molecular mechanisms of EIF5A2 related to tumorigenesis will also be discussed.     

Overcoming resistance to rapalogs in gliomas by combinatory therapies

Glioblastoma is the most common and aggressive brain tumor type, with a mean patient survival of approximately 1 year. Many previous analyses of the glioma kinome have identified key deregulated pathways that converge and activate mammalian target of rapamycin (mTOR). Following the identification and characterization of mTOR-promoting activity in gliomagenesis, data from preclinical studies suggested the targeting of mTOR by rapamycin or its analogs (rapalogs) as a promising therapeutic approach. However, clinical trials with rapalogs have shown very limited efficacy on glioma due to the development of resistance mechanisms. Analysis of rapalog-insensitive glioma cells has revealed increased activity of growth and survival pathways compensating for mTOR inhibition by rapalogs that are suitable for therapeutic intervention. In addition, recently developed mTOR inhibitors show high anti-glioma activity. In this review, we recapitulate the regulation of mTOR signaling and its involvement in gliomagenesis, discuss mechanisms resulting in resistance to rapalogs, and speculate on strategies to overcome resistance. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).     

Interaction studies of muts and mutl with DNA containing the major cisplatin lesion and its mismatched counterpart under equilibrium and nonequilibrium conditions

The DNA mismatch repair (MMR) system participates in cis‐diamminedichloroplatinum (II) (cisplatin) cytotoxicity through signaling of cisplatin DNA lesions by yet unknown molecular mechanisms. It is thus of great interest to determine whether specialized function of MMR proteins could be associated with cisplatin DNA damage. The major cisplatin 1,2‐d(GpG) intrastrand crosslink and compound lesions arising from misincorporation of a mispaired base opposite either platinated guanine of the 1,2‐d(GpG) adduct are thought to be critical lesions for MMR signaling. Previously, we have shown that cisplatin compound lesion with a mispaired thymine opposite the 3′ platinated guanine triggers new Escherichia coli MutS ATP‐dependent biochemical activities distinguishable from those encountered with DNA mismatch consistent with a role of this lesion in MMR‐dependent signaling mechanism. In this report, we show that the major cisplatin 1,2‐d(GpG) intrastrand crosslink does not confer novel MutS postrecognition biochemical activity as studied by surface plasmon resonance spectroscopy. A fast rate of MutS ATP‐dependent dissociation prevents MutL recruitment to the major cisplatin lesion in contrast to cisplatin compound lesion which authorized MutS‐dependent recruitment of MutL with a dynamic of ternary complex formation distinguishable from that encountered with DNA mismatch substrate. We conclude that the mode of cisplatin DNA damage recognition by MutS and the nature of MMR post‐recognition events are lesion‐dependent and suggest that MMR signaling through the major cisplatin lesion is unlikely to occur. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 636–647, 2013.     

Effect of Liraglutide on endoplasmic reticulum stress in diabetes

Endoplasmic reticulum (ER) stress is associated with the development of diabetes. The present study sought to investigate the effect of Liraglutide, a glucagon like peptide 1 analogue, on ER stress in β-cells. We found that Liraglutide protected the pancreatic INS-1 cells from thapsigargin-induced ER stress and the ER stress associated cell apoptosis, mainly by suppressing the PERK and IRE1 pathways. We further tested the effects of Liraglutide in the Akita mouse, an ER-stress induced type 1 diabetes model. After administration of Liraglutide for 8 weeks, p-eIF2α and p-JNK were significantly decreased in the pancreas of the Akita mouse, while the treatment showed no significant impact on the levels of insulin of INS-cells. Taken together, our findings suggest that Liraglutide may protect pancreatic cells from ER stress and its related cell death.