bims-aporos Biomed news
on Apoptosis and reactive oxygen species
Issue of 2018‒07‒15
six papers selected by
Gavin McStay
Staffordshire University


  1. Integr Comp Biol. 2018 Jul 05.
    Jimenez AG.
      All aerobic organisms are subjected to metabolic by-products known as reactive species (RS).RS can wreak havoc on macromolecules by structurally altering proteins and inducing mutations in DNA, among other deleterious effects. . To combat accumulating damage, organisms have an antioxidant system to sequester RS before they cause cellular damage. The balance between RS production, antioxidant defences, and accumulated cellular damage is termed oxidative stress. Physiological ecologists, gerontologists and metabolic biochemists have turned their attention to whether oxidative stress is the principal, generalized mechanism that mediates and limits longevity, growth rates and other life-history trade-offs in animals, as may be the case in mammals and birds. At the crux of this theory lies the regulation and activities of the mitochondria with respect to the organism and its metabolic rate. At the whole-animal level, evolutionary theory suggests that developmental trajectories and growth rates can shape the onset and rate of aging. Mitochondrial function is important for aging since it is the main source of energy in cells, and the main source of RS. Altering oxidative stress levels, either increases in oxidative damage or reduction in antioxidants, has proven to also decrease growth rates, which implies that oxidative stress is a cost of, as well as a constraint on, growth. Yet, in nature, many animals exhibit fast growth rates that lead to higher loads of oxidative stress, which are often linked to shorter lifespans. In this paper, I summarize the latest findings on whole-animal life history trade-offs, such as growth rates and longevity, and how these can be affected by mitochondrial cellular metabolism, and oxidative stress.
    DOI:  https://doi.org/10.1093/icb/icy090
  2. Free Radic Biol Med. 2018 Jul 04. pii: S0891-5849(18)31137-7. [Epub ahead of print]
    Xu K, Yao H, Hu J, Zhou J, Zhou L, Wei S.
      In photodynamic therapy (PDT), the elevated glutathione (GSH) of cancer cells have two sides for treatment efficacy, activation pre-drug by removing activity suppressor part (advantages) and consumption reactive oxygen species (ROS) to confer PDT resistance (disadvantages). Preparation all-in-one system by simple method to make best use of the advantages and bypass the disadvantages still were remains a technical challenge. Herein, we report a robust PDT nanoparticle with above function based on a self-assembled pyridine modified Zinc phthalocyanine (ZnPc-DTP). The activity suppressor and active part of ZnPc-DTP were linked by disulfide bond. After targeting cancer cells, GSH can react with ZnPc-DTP nanoparticles by cutting disulfide bond to release its active part (ZnPc-SH) and oxidize GSH. In vitro and in vivo results indicated that ZnPc-SH can effective suppress tumor growth under the low antioxidant tumor microenvironment (TME).
    Keywords:  Antioxidant; Drug activation; Glutathione; Photodynamic therapy; Self-assembled nanoparticles
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2018.06.030
  3. Microbes Infect. 2018 Jul 05. pii: S1286-4579(18)30144-8. [Epub ahead of print]
    Paik S, Choi S, Lee KI, Back YW, Son YJ, Jo EK, Kim HJ.
      Mycobacterial acyl carrier protein (AcpM; Rv2244) is a meromycolate extension acyl carrier protein of Mycobacterium tuberculosis, which participates in multistep mycolic acid biosynthesis. However, the function of AcpM in host-mycobacterium interactions during infection remains largely uncharacterized. Here we show that AcpM inhibits host cell apoptosis during mycobacterial infection. To examine the function of AcpM during infection, we generated a recombinant Mycobacterium smegmatis (M. smegmatis) strain overexpressing AcpM (Ms_AcpM) and a strain transformed with an empty vector (Ms_Vec). Ms_AcpM promoted intracellular survival of M. smegmatis and led to a significant decrease in the death rate of primary bone marrow-derived macrophages (BMDMs). Importantly, Ms_AcpM showed significantly decreased reactive oxygen species (ROS) generation and activation of c-Jun N-terminal kinase (JNK) signaling compared with Ms_Vec. In addition, treatment of BMDMs with recombinant AcpM significantly inhibited the apoptosis and ROS/JNK signaling induced by M. smegmatis. Moreover, recombinant AcpM enhanced intracellular survival of H37Rv. Taken together, these results indicate that AcpM plays a role as a virulence factor by modulating host cell apoptosis during mycobacterial infection.
    Keywords:  Mycobacterium smegmatis; Mycobacterium tuberculosis; acyl carrier protein; apoptosis; c-Jun N-terminal kinase; reactive oxygen species
    DOI:  https://doi.org/10.1016/j.micinf.2018.06.005
  4. Pflugers Arch. 2018 Aug;470(8): 1181-1192
    Tepikin AV.
      Cellular organelles form multiple junctional complexes with one another and the emerging research area dealing with such structures and their functions is undergoing explosive growth. A new research journal named "Contact" has been recently established to facilitate the development of this research field. The current consensus is to define an organellar junction by the maximal distance between the participating organelles; and the gap of 30 nm or less is considered appropriate for classifying such structures as junctions or membrane contact sites. Ideally, the organellar junction should have a functional significance, i.e. facilitate transfer of calcium, sterols, phospholipids, iron and possibly other substances between the organelles (Carrasco and Meyer in Annu Rev Biochem 80:973-1000, 2011; Csordas et al. in Trends Cell Biol 28:523-540, 2018; Phillips and Voeltz in Nat Rev Mol Cell Biol 17:69-82, 2016; Prinz in J Cell Biol 205:759-769, 2014). It is also important to note that the junction is not just a result of a random organelle collision but have active and specific formation, stabilisation and disassembly mechanisms. The nature of these mechanisms and their role in physiology/pathophysiology are the main focus of an emerging research field. In this review, we will briefly describe junctional complexes formed by cellular organelles and then focus on the junctional complexes that are formed by mitochondria with other organelles and the role of these complexes in regulating Ca2+ signalling.
    Keywords:  Ca2+ signalling; Endoplasmic reticulum; Membrane contact sites; Mitochondria; Organellar junctions; Reactive oxygen species
    DOI:  https://doi.org/10.1007/s00424-018-2179-z
  5. J Mol Cell Cardiol. 2018 Jul 05. pii: S0022-2828(18)30400-0. [Epub ahead of print]
    Liu W, Zhai X, Wang W, Zheng B, Zhang Z, Fan X, Wang J, Chen Y.
      Cyclophosphamide (CY)-induced acute cardiotoxicity is a common side effect which is dose dependent. It is reported that up to 20% of patients received high dose of CY treatment suffered from acute cardiac dysfunction. However, the effective intervention strategies and related mechanisms are still largely unknown. We aimed to investigate the effects of aldehyde dehydrogenase 2 (ALDH2), an important endogenous cardioprotective enzyme, on CY-induced acute cardiotoxicity and the underlying mechanisms. It was found that ALDH2 knockout (KO) mice were more sensitive to CY-induced acute cardiotoxicity, presenting as higher serum levels of creatine kinase-MB isoform and lactate dehydrogenase, and significantly reduced myocardial contractility compared with C57BL/6 (WT) mice. In addition, cardiac cell death, especially necrosis, was obviously increased in ALDH2 KO mice compared with WT mice after CY treatment. Furthermore, accumulation of toxic aldehydes such as acrolein and 4-HNE and reactive oxygen species (ROS) in the myocardium were significantly elevated after CY in ALDH2 KO mice. Importantly, ALDH2 activation by Alda-1 pretreatment markedly attenuated CY-induced accumulation of toxic aldehydes, cardiac cell death and cardiac dysfunction, without affecting CY's anti-tumor efficacy. In conclusion, the cardioprotective effects of ALDH2 activation against CY-induced acute cardiotoxicity are exerted via reducing toxic aldehydes accumulation and potentially interrupting the acrolein-ROS-aldehydes vicious circles, and thus alleviates myocardial cell death, without antagonizing the anti-tumor efficacy of CY. Therefore, ALDH2 might be a promising prevention and treatment target for CY-induced acute cardiotoxicity.
    Keywords:  Aldehyde dehydrogenase 2 (ALDH2); Cell death; Cyclophosphamide-induced acute cardiotoxicity; Toxic aldehydes
    DOI:  https://doi.org/10.1016/j.yjmcc.2018.07.006
  6. Fitoterapia. 2018 Jul 05. pii: S0367-326X(18)30916-X. [Epub ahead of print]129 179-184
    Ma YQ, Liu MH, Jiang K, Guo L, Qu SJ, Wan YQ, Tan CH.
      The fruits of Swietenia macrophylla (skyfruits) are commercially used as healthcare products to improve blood circulation. An investigation of active ingredients of skyfruits led to the isolation of four new limonoids, swietemacrolides A-D (1-4), together with ten known limonoids (5-14) and one proto-limonoid (15). Their structures were elucidated on the basis of MS and NMR data analysis. Swietemacrolide C (3) at the concentration of 10 μM showed significant protective effect on H2O2-induced apoptosis in human umbilical vascular endothelial cells (HUVECs), while swieteliacate D (5) displayed moderate anti-apoptotic activity.
    Keywords:  Antioxidant; Apoptosis; Human umbilical vein endothelial cells; Limonoids; Swietenia macrophylla
    DOI:  https://doi.org/10.1016/j.fitote.2018.07.001