bims-aporos Biomed news
on Apoptosis and reactive oxygen species
Issue of 2018‒10‒28
two papers selected by
Gavin McStay
Staffordshire University


  1. Free Radic Biol Med. 2018 Oct 17. pii: S0891-5849(18)31398-4. [Epub ahead of print]
    Liu SY, Song JY, Fan B, Wang Y, Pan YR, Che L, Sun YJ, Li GY.
      Retinal degeneration is a major cause of severe vision loss and irreversible blindness and is characterized by progressive damage to retinal photoreceptor cells. Resveratrol (RSV) serves as an activator of the histone deacetylase, Sirt1, and has been shown to exert anti-oxidative properties. In this study, we mimicked retinal degeneration by subjecting photoreceptors (661W cells) to glucose deprivation (GD) or light exposure. Under these conditions, we investigated the mechanisms underlying GD- or light exposure-induced cell death and the protective effect of RSV. We found that GD and light exposure resulted in mitochondrial dysfunction, oxidative stress, and cell death. Treatment of injured cells with RSV decreased the production of reactive oxygen species (ROS), improved the ratio of reduced/oxidized glutathione (GSH/GSSG), mitochondrial membrane potential and morphology, and reduced apoptosis. We used the caspase inhibitor, z-VAD-fmk, and a lentiviral-mediated shRNA knockdown of PARP-1 to reveal that GD and light exposure-induced cell death have different underlying mechanisms; GD triggered a caspase-dependent cell death pathway, whereas light exposure triggered a PARP-dependent cell death pathway. The level of caspase-9 and caspase-3, upregulated following GD, were reduced by treatment with RSV. Similarly, the level of PARP-1 and AIF, upregulated following light exposure, were decreased by treatment with RSV. Additionally, treatment with RSV elevated the protein expression and enzymatic activity of Sirt1 and a Sirt1 inhibitor reduced the protective effect of RSV against insult-induced cellular injuries, indicating that RSV's protective effect may involve Sirt1 activation. Finally, we investigated the neuroprotection of RSV in vivo. Administration of RSV to mice under extreme light exposure led to a suppression of the light-induced thinning of the outer nuclear layer (ONL) detected by H&E staining and restored retinal function evaluated by electroretinography (ERG). Taken together, our findings provide evidence that treatment with RSV has neuroprotective effects on both GD and light exposure-induced cell death pathways in photoreceptor cells.
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2018.10.431
  2. World Neurosurg. 2018 Oct 17. pii: S1878-8750(18)32355-6. [Epub ahead of print]
    Xie Q, Liu M, Yan YF, Shen X, Wang ES.
      BACKGROUD: Tetranectin is a secreted homotrimeric protein belonging to the C-type lectin family. Our previous studies found that tetranectin was not only related to, but also played a protective role in Parkinson's disease. In this study, we aim to illustrate the molecular mechanism of the secreted tetranectin.METHODS: We used exogenous tetranectinto investigate the function and molecular mechanism of secreted tetranectin in a 1-methyl-4-phenylpyridine (MPP+)-induced SH-SY5Y cell model. Cell viability and reactive oxygen species were measured to assess the protective effects of tetranectin against MPP+. Apoptosis was measured in several aspects including Bcl-2/Bax expression, caspase-3/7 activity, Annexin V staining, and nuclear morphology. Autophagy was measured as LC3 expression and autophagy flux. Moreover, we used cell immunofluorescence to detect the transport of tetranectin. Western blotting was performed to measure the phosphorylation level of P70S6K1, and co-immunoprecipitation was applied to confirm the interaction between tetranectin and P70S6K1.
    RESULTS: The data showed exogenous tetranectin alleviated MPP+-induced toxicity, high reactive oxygen species levels, apoptosis, and autophagy, and changed the phosphorylation level of P70S6K1. Immunofluorescence images suggested exogenous tetranectin could be taken into SH-SY5Y cells and the co-immunoprecipitation experiment indicated tetranectin interacted with P70S6K1.
    CONCLUSION: Exogenous tetranectin protects against MPP+-induced neurotoxicity by promoting P70S6K1 phosphorylation once taken into SH-SY5Y cells.
    Keywords:  1-methyl-4-phenylpyridine; P70S6K1; Parkinson; neurotoxicity; tetranectin
    DOI:  https://doi.org/10.1016/j.wneu.2018.10.058