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Highlights: [•] LDH activity and apoptosis in TPEN-incubated neurons were markedly increased. [•] We confirmed that TPEN induces apoptosis of hippocampal neurons through inhibition of ERK pathway. [•] We show for the first time that activation of caspase-3 induced by TPEN in was mediated by ERK pathway. [ABSTRACT FROM AUTHOR]

Several biological processes as well as infectious agents, physiological or environmental stress, and perturbed antioxidant response can promote oxidative stress. Oxidative stress usually happens when cells are exposed to more electrically charged reactive oxygen species (ROS) such as HO or O . ROS are well known for being both beneficial and deleterious. Recent studies have indicated that ROS are deleterious to cells, leading to programmed cell death (PCD) at high concentrations. At low concentrations, however, ROS can act as signaling molecules in a variety of cellular processes. In this review, we present an update of our current understanding of the role and regulation of reactive oxygen species in various viral infections, cellular signaling pathways and immune responses. We then discuss how the antioxidant defense system acts as an antiviral effector to limit cell damage. [ABSTRACT FROM AUTHOR]

Background and Aim: Long noncoding RNA TRPM2‐AS has emerged as a novel regulator in cancer initiation and progression of various cancers. However, the function and underlying mechanism of TRPM2‐AS in the progression of gastric cancer (GC) remain poorly understood. Methods: GEO and TCGA databases were used for isolation of differential lncRNA expression. TRPM2‐AS expression levels in GC tissues and cells were measured by quantitative polymerase chain reaction method. TRPM2‐AS subcellular location was detected by fluorescence in situ hybridization analysis. The functional roles of TRPM2‐AS in cells were analyzed by loss and gain function assays. Results: By using bioinformatics and quantitative polymerase chain reaction methods, TRPM2‐AS expression levels were proved to be upregulated in GSE70880 dataset, TCGA database, and 26 GC tissues, which was partly induced by SP1. The results of clinical assays showed that TRPM2‐AS could be an indicator for early‐stage GC diagnosis. Fluorescence in situ hybridization analysis showed that TRPM2‐AS was located in both nucleus and cytoplasm. Functional experiments displayed that knockdown of TRPM2‐AS inhibited proliferation, migration, and invasion in GC cells. Furthermore, depression of TRPM2‐AS suppressed cell growth though promotion of cell apoptosis. The expression levels of cleaved PARP, caspase 9, caspase 3, and Bax were significantly increased in BGC823 with TRPM2‐AS knockdown. In addition, knockdown of TRPM2‐AS reduced and phosphorylate signal transducer and activator of transcription 3 and increased and phosphorylate p38 mitogen‐activated protein kinase. Conclusions: This study demonstrated that SP1‐regulated TRPM2‐AS is involved in GC cell apoptosis probably via p38 mitogen‐activated protein kinase and signal transducer and activator of transcription 3 pathways, indicating that TRPM2‐AS might be a potential therapeutic target in GC. [ABSTRACT FROM AUTHOR]

Salidroside, a natural active ingredient extracted from Rhodiola rosea , has been shown to exert antitumor activity against breast cancer Dong Young et al. [ 1 ], colon cancer Sun et al. [ 2 ] and bladder cancer Tian et al. [ 3 ]. However, the effect of salidroside on apoptosis and autophagy in gastric cancer remains unclear. In our research, we observed the biological effect of salidroside on human gastric cancer AGS cells. Our results demonstrated that salidroside inhibited the growth of AGS cells both in vivo and in vitro and exerted a proapoptotic effect on AGS cells as confirmed by flow cytometry, Hoechst staining and western blot analysis. Additionally, we found that salidroside decreased the phosphorylation of PI3K and Akt and that pretreatment with the PI3K/Akt agonist IGF-1 could weaken the proapoptotic effect of salidroside. Interestingly, the exposure of AGS cells to salidroside induced autophagy as indicated by transmission electron microscopy, mRFP-GFP-LC3 transfection and western blot analysis, suggesting that salidroside promoted autophagy in gastric cancer AGS cells. Furthermore, treatment with the autophagy inhibitor chloroquine enhanced salidroside-induced cell apoptosis, indicating that the autophagy mediated by salidroside may protect AGS cells from death. Additionally, we found that salidroside decreased the level of p-mTOR protein in a concentration-dependent manner and that pretreatment with IGF-1 decreased the expression of autophagy proteins, suggesting that salidroside induced autophagy through the PI3K/Akt/mTOR pathway. The above findings indicate that salidroside inhibited the growth of gastric cancer and induced apoptosis and protective autophagy through the PI3K/Akt/mTOR pathway. In summary, our study provides novel insights regarding the activity of salidroside against gastric cancer and contributes to the clinical application of salidroside combined with autophagy inhibitors as a chemotherapeutic strategy for human gastric cancer. [ABSTRACT FROM AUTHOR]

An experiment was performed to observe the changes in Raf-1 kinase/mitogen-activated protein kinase ERK (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways in cultured hippocampal neurons and its correlation with neurons apoptosis induced by intracellular zinc depletion. Cultured hippocampal neurons were exposed to a cell membrane-permeant zinc chelator TPEN (2 µM), and to TPEN plus zinc sulfate (5 µM) for 24 h. Cultures were then processed to detect neuronal viability by the methyl thiazolyl tetrazolium assay, while apoptosis rate was simultaneously observed by the flow cytometric analysis. Caspase-3, Raf-1, pMEK, pERK1/2, and pCREB protein levels were examined by Western blot assays. The viability in TPEN-incubated neurons was notably decreased, apoptosis rate and expression of caspase-3 significantly increased compared to untreated controls. The significant down-regulation of Raf/MEK/ERK signaling pathway and expression of pCREB were decreased in TPEN-treated neurons. Co-addition of zinc almost completely reversed TPEN-induced alterations described. The results demonstrated zinc-modulated apoptosis and the expression of Raf/MEK/ERK at the protein level in hippocampal neurons. It is possible that zinc depletion-induced apoptosis in cultured hippocampal neurons may be relevant to the changes of Raf/MEK/ERK signaling pathway. [ABSTRACT FROM AUTHOR]