bims-aporos Biomed news
on Apoptosis and reactive oxygen species
Issue of 2018‒08‒19
four papers selected by
Gavin McStay
Staffordshire University


  1. Pharmacology. 2018 Aug 10. 102(3-4): 213-222
    Gu XL.
      AIM: To investigate the regulation of microRNA-124 -(miRNA-124) on NF-κB pathway from H2O2-induced apoptosis and oxidative stress in human lens epithelial cells (hLEC).METHODS: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to detect hLEC -viability. HLECs were divided into Blank, H2O2, mimics (miRNA-124 mimics) + H2O2, NC+ H2O2, pyrrolidine dithiocarbamate (PDTC; NF-κB signaling pathway inhibitor) + H2O2, and inhibitors (miRNA-124 inhibitors) + PDTC + H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, Dichloro-dihydro-fluorescein diacetate to measure reactive oxygen species (ROS) production, and AnnexinV-FITC/PI staining to determine cell apoptosis. The mitochondrial membrane potential (MMP) was detected by fluorescence probe JC-1.
    RESULTS: The H2O2-induced hLEC showed reductions in cell viability with decreased miRNA-124 but increased p-p65 in a dose-/time-dependent manner. Furthermore, ROS production, malondialdehyde content, Bax and Caspase-3 expressions, and cell apoptosis were elevated in H2O2-induced hLEC, whereas the activities of superoxide dismutase and glutathione peroxidase, Bcl-2 expression, MMP, as well as the mitochondrial energy metabolism genes were reduced. Additionally, miRNA-124 mimics and PDTC both decreased the p-p65 and reversed the cytotoxicity in H2O2-induced hLEC.
    CONCLUSION: MiRNA-124 prevents H2O2-induced oxidative stress and apoptosis in hLEC through suppressing the activation of the NF-κB pathway.
    Keywords:  Apoptosis; Human lens epithelial cells; MicroRNA-124; NF-κB; Oxidative stress
    DOI:  https://doi.org/10.1159/000491433
  2. J Photochem Photobiol B. 2018 Aug 06. pii: S1011-1344(18)30456-1. [Epub ahead of print]187 76-88
    Wang XZ, Jia Z, Yang HH, Liu YJ.
      A new series of dibenzoxanthene derivatives 4a-4d (4a: 1-oxo-5-bromo-11-cyano-13c-methoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene, 4b: 1-oxo-5-bromo-11-cyano-13c-ethoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene, 4c: 1-oxo-5-bromo-11-cyano-13c-propoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene and 4d: 1-oxo-5-bromo-11-cyano-13c-butoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene) were synthesized and the molecular mechanisms of anti-cancer activities were investigated. These compounds showed excellent anti-tumor activity against A549, Eca-109, HeLa, HepG2 and SGC-7901 cell lines. Compounds 4a-4d could effectively inhibit the migration and invasion of HeLa cells in wound healing and transwell assays. Compounds induced the DNA damage and arrested in cell cycle distribution at G0/G1 phase. Apoptosis induced by compounds was detected using morphological observation of nuclear changes and FITC-Annexin V/PI staining. Additionally, compounds also induced the autophagy of HeLa cells through observing AO staining and upregulated the expression of LC3II and Beclin-1 proteins. Furthermore, treatment with autophagy inhibitor 3-methyladenine induced an obvious decrease in apoptotic rate in HeLa cells. This indicated that autophagy further promoted the HeLa cells apoptosis. Compounds 4a-4d enhanced the intracellular Ca2+ and ROS. Then the mitochondrial membrane potential of HeLa cells was depolarized and the cytochrome C was released from mitochondria into cytoplasm. Activities of the apoptotic factors Bcl-2, Bax, caspase-3 were measured using western blotting. After HeLa cells were exposed to compounds, the expressions of PI3K and Akt protein were decreased. Compounds exhibit anti-cancer activity via apoptosis and autophagy through inhibition of PI3K/Akt signaling pathway in HeLa cells.
    Keywords:  Apoptosis; Autophagy; Cytotoxicity; Dibenzoxanthenes; PI3K/Akt signaling pathway
    DOI:  https://doi.org/10.1016/j.jphotobiol.2018.08.001
  3. Pharmacology. 2018 Aug 10. 102(3-4): 196-205
    Xie C, Liu L, Wang Z, Xie H, Feng Y, Suo J, Wang M, Shang W, Feng G.
      OBJECTIVES: Icariin (ICA) is a bioactive flavonoid with renal protective actions. This study investigated the effects of ICA on renal injury, inflammation, oxidative damage, apoptosis, and survival in a mouse model of cecal ligation and perforation (CLP)-induced sepsis.METHODS: Sepsis was induced by CLP. Mice were treated with ICA (30 or 60 mg/kg) for 3 days before CLP. Renal functions, inflammatory responses, oxidative damage, histological changes, apoptosis, and vascular permeability were examined. The effects of ICA on CLP-induced expression of renal nuclear factor-κB (NF-κB), cleaved caspase-3, Bax, and Bcl-2 were evaluated.
    RESULTS: Mice in the CLP group had a low survival rate and increases in blood urea nitrogen and creatinine levels, proinflammatory cytokine levels, oxidative damage, apoptosis, and vascular permeability. These renal changes were dramatically improved by ICA treatment, especially in the 60 mg/kg ICA group. The detection of molecules involved in the inflammation and apoptosis of the kidney indicated that ICA reduced expression of NF-κB, cleaved caspase-3, and Bax but enhanced expression of Bcl-2.
    CONCLUSION: ICA improves CLP-induced mortality and acute kidney injury by inhibiting renal oxidant damage, inflammatory responses, apoptosis, and vascular permeability.
    Keywords:  Apoptosis; Icariin; Inflammation; Kidney; Oxidative damage; Sepsis
    DOI:  https://doi.org/10.1159/000487955
  4. Chemosphere. 2018 Aug 03. pii: S0045-6535(18)31478-4. [Epub ahead of print]211 648-652
    Dong WQ, Sun HJ, Zhang Y, Lin HJ, Chen JR, Hong HC.
      Low concentrations of arsenic (As) contamination in aquatic environment is a worldwide issue, which is of great concern. To evaluate the impact of low concentrations of As on zebrafish, we measured the growth, antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT), oxidative damage (malondialdehyde, MDA) and apoptosis-related genes (nrf2, p53 and c-jun) of adult zebrafish after exposing to different AsIII concentrations (0, 10, 50, 100 or 150 μg L-1) for 28 d. Results indicated that exposure to low AsIII concentrations decreased the zebrafish weight by 14%, increased the activities of SOD and CAT by 23-41% and 31-59%, decreased the contents of MDA by 29-54%, and modulated transcription of apoptosis related genes. Our study showed that chronic exposure to AsIII concentrations <150 μg L-1 generated oxidative stress and damage on zebrafish, and altered apoptosis-related genes in zebrafish.
    Keywords:  Apoptosis; Arsenite; Oxidative damage; Oxidative stress; Zebrafish
    DOI:  https://doi.org/10.1016/j.chemosphere.2018.08.010