bims-aporos Biomed news
on Apoptosis and reactive oxygen species
Issue of 2018‒09‒23
six papers selected by
Gavin McStay
Staffordshire University

  1. Biomed Pharmacother. 2018 Sep 12. pii: S0753-3322(18)32104-8. [Epub ahead of print]108 137-143
    Zhao J, Zhang G, Li M, Luo Q, Leng Y, Liu X.
      Excessive production of amyloid β (Aβ) induced by familial mutations in amyloid precursor protein (APP) and presenilin 1 (PS1) results in neuronal oxidative insults, mitochondrial dysfunction, and apoptosis, which play an essential role in the pathological development of Alzheimer's disease (AD). Aloperine, a quinolizidine alkaloid derived from the leaves of the Sophora plant, has displayed multiple pharmacological functions in several chronic diseases. In the current study, we investigated the neuro-protective effects of aloperine against cytotoxicity in mouse Neuro2a (N2a) cells transfected with Swedish amyloid precursor protein (Swe-APP) mutant and presenilin 1 exon 9 deletion mutant (N2a/Swe.D9). We found that aloperine ameliorated oxidative stress patterns in N2a/Swe.D9 cells by reducing the production of reactive oxygen species (ROS) and 4-hydroxy-2-nonenal (4-HNE). Additionally, aloperine treatment led to elevated generation of ATP and increased mitochondrial membrane potential (MMP) in N2a/Swe.D9 cells. Importantly, we found that aloperine treatment reduced the vulnerability of N2a/Swe.D9 cells to H2O2. Aloperine also inhibited apoptosis of N2a/Swe.D9 cells via a mitochondria-dependent pathway. These findings suggest that aloperine may have pharmacological potential for the treatment of AD.
    Keywords:  Aloperine; Alzheimer’s disease; Amyloid β; Apoptosis; Mitochondrial dysfunction; Oxidative stress
  2. Int Immunopharmacol. 2018 Sep 12. pii: S1567-5769(18)30596-4. [Epub ahead of print]64 256-263
    Lv T, Shen L, Yang L, Diao W, Yang Z, Zhang Y, Yu S, Li Y.
      BACKGROUND: Inflammation, oxidative stress and epithelial barrier dysfunction have been implicated in inflammatory bowel disease (IBD) pathology. The targeted inhibition of these features may represent a promising therapeutic strategy for IBD. Polydatin is an effective natural antioxidant that possesses strong antioxidant and anti-apoptotic properties. Thus, we studied the protective effects of polydatin treatments on a mouse model of experimental colitis.METHODS: Acute colitis was experimentally induced by adding 3% dextran sulfate sodium (DSS) to the drinking water provided to mice for 7 days and by administering different doses of polydatin (15, 30, or 45 mg/kg) during the same period. Mice were also treated with the Sonic hedgehog (Shh) pathway inhibitor cyclopamine to estimate the efficacy of polydatin and Shh inhibitors on colitis. The disease activity index (DAI), colon length, histology, levels of oxidative and apoptotic mediators and levels of Shh pathway components were evaluated.
    RESULTS: The polydatin treatment significantly attenuated the DAI, colon shortening and histological damage. In addition, polydatin administration effectively decreased malondialdehyde (MDA) levels and increased the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Polydatin also inhibited apoptosis in mice with colitis by downregulating the expression of the pro-apoptotic proteins Bax, caspase 3 and cleaved caspase 3 and increasing the expression of the anti-apoptotic protein Bcl-2. Furthermore, polydatin modulated Shh signaling pathway activation. After polydatin treatment, the main components of the Shh pathway, including Shh, Patched (Ptc), Smoothened (Smo), and glioblastoma-1 (Gli1), were upregulated at the mRNA and protein levels. Blockade of the Shh pathway using cyclopamine abolished the effects of polydatin on mice with colitis.
    CONCLUSION: Based on these observations, polydatin may suppress experimental colitis at least partially by regulating the Shh signaling pathway.
    Keywords:  Apoptosis; Oxidative stress; Polydatin; Sonic hedgehog pathway; Ulcerative colitis
  3. J Agric Food Chem. 2018 Sep 16.
    Han L, Yang Q, Ma W, Li J, Qu LZ, Wang M.
      Protocatechuic acid (PCA, 3, 4-dihydroxybenzoic acid), the main metabolite of anthocyanins, is widely distributed in fruits and vegetables, and has been reported to possess a strong antioxidant activity. Herein, we aimed to investigate the protective effect of PCA against high palmitic acid-induced oxidative damage and the underling molecular mechanisms in human umbilical vein endothelial cells (HUVECs). PCA reduced the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of endogenous antioxidant enzymes including superoxide dismutases (SOD), glutathione peroxidases-1 (Gpx-1), and heme oxygenase-1 (HO-1). Metabolomic analysis showed that PCA affected numerous metabolites, especially some of which were related with energy metabolism. PCA also up-regulated the phosphorylation of AMPK at Thr172 through activating LKB1, then promoted the expression of p-Nrf2 and HO-1. Moreover, PCA reversed the decreased expression of PGC-1α and significantly increased the mitochondrial density. Collectively, these results demonstrated that PCA attenuated PA-induced oxidative damage in HUVECs via an AMPK-dependent pathway.
  4. Free Radic Biol Med. 2018 Sep 12. pii: S0891-5849(18)31584-3. [Epub ahead of print]
    Mu HN, Li Q, Fan JY, Pan CS, Liu YY, Yan L, Sun K, Hu BH, Huang DD, Zhao XR, Chang X, Wang CS, He SY, He K, Yang BX, Han JY.
      The transplanted liver inevitably suffers from ischemia reperfusion (I/R) injury, which represents a key issue in clinical transplantation determining early outcome and long-term graft survival. A solution is needed to deal with this insult. This study was undertaken to explore the effect of Caffeic acid (CA), a naturally occurring antioxidant, on I/R injury of grafted liver and the mechanisms involved. Male Sprague-Dawley rats underwent orthotopic liver transplantation (LT) in the absence or presence of CA administration. In vitro, HL7702 cells were subjected to hypoxia/reoxygenation. LT led to apparent hepatic I/R injury, manifested by deteriorated liver function, microcirculatory disturbance and increased apoptosis, along with increased PDIA3 expression and nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase activity, and membrane translocation of NADPH oxidase subunits. Treatment with CA attenuated the above alterations. siRNA-mediated knockdown of PDIA3 in HL7702 cells and rats played the same role as CA not only in inhibiting ROS production and NADPH oxidase activity, but also in alleviating hepatocytes injury. CA protects transplanted livers from injury, which is likely attributed to its protection of oxidative damage by interfering in PDIA3-dependent activation of NADPH oxidase.
    Keywords:  Apoptosis; Liver microcirculatory disturbance; Salvia miltiorrhiza; Superoxide anion
  5. Exp Mol Pathol. 2018 Sep 12. pii: S0014-4800(18)30178-3. [Epub ahead of print]
    Yang ZB, Chen WW, Chen HP, Cai SX, Lin JD, Qiu LZ.
      OBJECTIVE: Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is confirmed to play crucial roles in septic liver injury. The present study aims to investigate the mechanisms of miR-155 in septic liver injury.METHODS: The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) in mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+ miR-155 antagomir. The survival rate and body weight were monitored. Liver injury was assessed by H&E staining. The levels of serum ALT and inflammatory cytokines were determined by ELISA kits. Oxidative stress was detected by MDA and SOD detection kits. The miR-155, Nrf-2, and markers related to oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial injury and apoptosis were detected by western blotting and qPCR. Apoptosis in liver tissues was detected by TUNELstaining.
    RESULTS: MiR-155 antagomir alleviated liver injury as evidenced by enhancing survival rate and body weight, inhibiting inflammatory cell infiltration, liver cells necrosis and decreasing ALT level. The productions of TNF-α, IL-6 were suppressed, while anti-inflammatory cytokine IL-10 was promoted by miR-155 antagomir. Oxidative stress was inhibited by miR-155 antagomir via enhancing nuclear factor, erythroid 2-like 2 (Nrf-2) expression. ER stress and Cytochrome C (Cyto-C) release were restrained by miR-155 antagomir. Sepsis-induced apoptosis was repressed by miR-155 antagomir as manifested by the decreased levels of Bax, cleaved caspase-12, 9 and 3, and increased levels of Bcl-2 and uncleaved PARP.
    CONCLUSION: MiR-155 antagomir relieved septic liver injury through inhibiting oxidative stress-mediated ER stress, mitochondrial dysfunction and apoptosis via targeting Nrf-2, suggesting miR-155 as a therapeutic target for septic liver injury.
    Keywords:  ER stress; MiR-155; Nrf-2; Oxidative stress; Septic liver injury
  6. Mol Aspects Med. 2018 Oct;pii: S0098-2997(18)30087-6. [Epub ahead of print]63 1-2