bims-aporos Biomed news
on Apoptosis and reactive oxygen species
Issue of 2018‒09‒30
six papers selected by
Gavin McStay
Staffordshire University


  1. J Stroke Cerebrovasc Dis. 2018 Sep 19. pii: S1052-3057(18)30262-3. [Epub ahead of print]
    Song XY, Hu JF, Wu DH, Ji HJ, Chen NH.
      IMM-H004 [7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin] is a novel derivative of coumarin, which played neuroprotective roles in brain ischemia in rats in previous studies. Although antiapoptosis and improving synapsis structure were proved, the effects and mechanisms of IMM-H004 in brain ischemia need further study. In this paper, the effect of IMM-H004 on H2O2-induced neurotoxicity in pheochromocytoma (PC12) cells was researched. Morphological observation, MTT method and PI/Hoechst staining were used to indicate cell viability and apoptosis. JC-1 and DCFH-DA were used to test mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), respectively. The antioxidative activity was detected by Glutathione (GSH) and Total Antioxidant Capacity (TAC) Assay kits. Western blot was used to test apoptosis related proteins. Our results showed that treatment with 1-10 μM IMM-H004 markedly increased cell viability and decreased cell apoptosis induced by H2O2. Moreover, 1-10 μM IMM-H004 could enhance MMP and protect mitochondrial function. 1-10 μM IMM-H004 also could lower the ROS and raise the GSH and TAC level. Furthermore, 1-10 μM IMM-H004 could decrease the ratio of Bax/Bcl-2 and increase the ratio of p-AKT/AKT, which were related to apoptosis and survival. All these indicated that IMM-H004 protects PC12 cells against H2O2-induced neurotoxicity. Antioxidative and antiapoptosis may be the mechanisms of IMM-H004 in brain ischemia. These studies indicate that IMM-H004 might be a potential drug for treatment brain ischemia.
    Keywords:  IMM-H004; apoptosis; coumarin; hydrogen peroxide; oxidative stress
    DOI:  https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.022
  2. Cell Signal. 2018 Sep 20. pii: S0898-6568(18)30231-6. [Epub ahead of print]53 14-21
    Hwang HJ, Jung TW, Kim JW, Kim JA, Lee YB, Hong SH, Roh E, Choi KM, Baik SH, Yoo HJ.
      Protectin DX (PDX), which is a novel regulator of 5' adenosine monophosphate-activated protein kinase (AMPK), has recently gained attention for its ability to improve several metabolic diseases. However, the function of PDX in vascular endothelial cells remains unclear. To confirm the protective effects of PDX on endothelial oxidative stress, human umbilical vein endothelial cells (HUVECs) were treated with hydroperoxide (H2O2) and PDX. PDX treatment significantly increased the level of AMPK phosphorylation, and this elevation was attenuated after treatment with G-protein coupled receptor 120 (GPR120) antagonist or GPR120 knockdown. Expressions and activities of antioxidant proteins, including catalase and superoxide dismutase 2 (SOD2), were elevated by PDX and were inhibited by treatment with AMPK inhibitor or with GPR120 antagonist. Production of H2O2-induced reactive oxygen species (ROS), the Bax/Bcl-2 ratio, and the loss of mitochondrial membrane potential were all reversed by PDX, leading to improved cell viability and reduced release of lactate dehydrogenase (LDH). Using flow cytometry, we also found that PDX significantly reduced the H2O2-induced apoptotic population of cells. These protective effects of PDX were all reversed after treatment with AMPK inhibitor or GRP120 antagonist. These results show that the PDX-AMPK axis has a protective role against H2O2-induced oxidative stress in vascular endothelial cells.
    Keywords:  Apoptosis; Endothelial cells; Oxidative stress; Protectin DX
    DOI:  https://doi.org/10.1016/j.cellsig.2018.09.011
  3. Food Chem Toxicol. 2018 Sep 20. pii: S0278-6915(18)30684-7. [Epub ahead of print]
    Lang F, Qu J, Yin H, Li L, Zhi Y, Liu Y, Fang Z, Hao E.
      Z-Ligustilide is the most potent bioactive component of Angelica sinensis, which is widely used in Chinese traditional medicine. Z-Ligustilide selectively affected ovarian cancer cell survival in a dose dependent manner. Z-Ligustilide induced apoptotic cell death was determined by flow cytometry. We also demonstrated that apoptotic cell death was triggered by Z-Ligustilideinduced oxidative stress and mitochondria played an active role. Mitochondrial polarization was reduced by Z-Ligustilidewhereas mitochondrial superoxide formation was increased. NRF2 was induced by Z-Ligustilide in OVCAR-3 cells at epigenetic level and its downstream antioxidant defense genesHeme oxygenase-1,NAD(P)H Quinone Dehydrogenase 1, UDP Glucuronosyltransferase Family 1 Member A1and Glutamate-Cysteine Ligase. NRF2 knockdown by siRNA resulted increased cell death by Z-Ligustilide in ovarian cancer cells. Our result demonstrated the pro-survival role of NRF2 in Z-Ligustilide induced ovarian cancer cell death.
    Keywords:  Apoptosis; Ovarian cancer; ligustilide; mitochondria; oxidative stress
    DOI:  https://doi.org/10.1016/j.fct.2018.09.041
  4. Int J Biol Macromol. 2018 Sep 20. pii: S0141-8130(18)33174-X. [Epub ahead of print]
    Wang Y, Liu LL, Tian Y, Chen Y, Zha WH, Li Y, Wu FJ.
      Death-associated protein kinase 2 (DAPK2) has indicated functional roles in cellular processes, including survival, apoptosis, and autophagy. This study is aimed to identify the effect of DAPK2 on oxidative damage and apoptosis of placental cells in hypertensive disorder complicating pregnancy (HDCP) through mTOR pathway. Microarray-based gene expression analysis was performed to predict the differentially expressed genes related to HDCP. To investigate the specific mechanism of DAPK2 in HDCP cells, placental microvascular endothelial cells were treated with mimic or siRNA of DAPK2 and mTOR to detect the expression of related genes, cell autophagy and apoptosis and oxidative damage. Finally, rats were modeled with HDCP to verify the cell experiment results. DAPK2 was downregulated in HDCP, and could activate mTOR. Besides, DAPK2 overexpression led to decreases in autophagy in HPVECs as well as apoptosis and oxidative damage in placental cells indicated by a substantial decrease in Beclin-1, LC3 II/LC3 I and Bax along with an increase in Bcl-2, 4EBP1 and p70S6K. It also ameliorates blood pressure elevation in HDCP rats. The study defined remission effect of DAPK2 on placental cell oxidative damage and apoptosis in HDCP via mTOR activation. Together, DAPK2 regulating mTOR pathway presents a promising therapy for HDCP treatment.
    Keywords:  Apoptosis; Autophagy; Death-associated protein kinase 2; Human placental microvascular endothelial cells; Hypertensive disorder complicating pregnancy; Oxidative damage; Placental cells; mTOR signaling pathway
    DOI:  https://doi.org/10.1016/j.ijbiomac.2018.09.111
  5. Toxicol In Vitro. 2018 Sep 19. pii: S0887-2333(18)30568-X. [Epub ahead of print]
    Martínez-Morcillo S, Pérez-López M, Soler-Rodríguez F, González A.
      In the present study we employed cultured pancreatic stellate cells to study the effect of the organophosphorus insecticide dimethoate on pancreatic cell physiology. Esterase activity, cell viability, reactive oxygen species generation and Ca2+ mobilization were examined. Our results show that dimethoate (0.1, 1 and 10 μM) induced a concentration-dependent inhibition of cholinesterase enzymatic activity at all concentrations tested. A drop in carboxylesterase activity was noted in the presence of 10 μM dimethoate. In the presence of the pesticide a decrease in cell viability was detected. The clearer effect could be observed when the cells had been incubated during 96 h in the presence of dimethoate. The pesticide induced a slight but statistically significant increase in the production of reactive oxygen species in the mitochondria. Incubation of cells with dimethoate, in the presence of Ca2+ in the extracellular medium, led to a slow and progressive increase in [Ca2+]c towards an elevated value over the prestimulation level. A similar behavior was observed in the absence of extracellular Ca2+, indicating that dimethoate releases Ca2+ from the intracellular stores. Our results suggest that dimethoate might alter intracellular pathways that are critical for pancreatic physiology, creating a situation potentially leading to dysfunction in the exocrine pancreas.
    Keywords:  Calcium; Dimethoate; Esterase activity; Organophosphorus insecticide; Pancreatic stellate cells
    DOI:  https://doi.org/10.1016/j.tiv.2018.09.011
  6. Brain Res Bull. 2018 Sep 20. pii: S0361-9230(18)30519-7. [Epub ahead of print]
    Li W, Yang S, Yu FY, Zhao Y, Sun ZM, An JR, Ji E.
      Obstructive sleep apnea (OSA) is a very common breathing and sleep disorder characterized by intermittent hypoxia (IH), which is often associated with behavioral and neurocognitive functions impairment. Hydrogen (H2), as a novel and effective antioxidant, is reported to be a potential neuroprotective agent. The aim of this study is to investigate whether H2 could improve CIH-induced neurocognitive impairment and the related mechanism. Rats were exposed to IH for 5 weeks (8 h/day) and/or inhalation of H2 gas 2 h/day. Morris Water Maze test was used to appraise the spatial reference and working memory. The oxidative stress was evaluated through the level of MDA and SOD and apoptosis of hippocampal neurons was assayed with Bcl-2/Bax ratio and TUNEL staining. Our results showed that H2 treatment improved the CIH-induced spatial learning and memory impairments. Moreover, inhalation of H2 gas reduced the level of MDA and increased in the activity of SOD, indicating suppressed CIH-induced oxidative stress. In addition, H2 could increase expression of Bcl-2/Bax ratio and inhibited neurons apoptosis in hippocampus. In conclusion, these results suggest that inhalation of H2 could attenuate the CIH-induced neurocognitive functions impairment via anti-oxidant and anti-apoptosis effect. Additional, our findings may provide a potential therapeutic for neurocognitive diseases in patients with OSA.
    Keywords:  Apoptosis; Chronic intermittent hypoxia; Hydrogen; Neurocognitive impairment; Oxidative stress
    DOI:  https://doi.org/10.1016/j.brainresbull.2018.09.012