Oxygen Radical Induced Gastric Mucosal Cell Death: Apoptosis or Necrosis?

Abstract

Reactive oxygen species (ROS) and resultant oxidative damage is a common pathway for gastric mucosal injury. This study was undertaken to determine whether apoptosis or necrosis was responsible for hydrogen peroxide (a representative ROS)-induced gastric mucosal death and whether caspase cascade blockade could prevent this process. AGS cells (human gastric adenocarcinoma cells) were exposed to hydrogen peroxide (H(2)O(2)), 0.5-2 mM, from 6 to 24 h. Lactic dehydrogenase (LDH) measured necrosis, whereas Caspase-3 and PARP activation and DNA-histone complex formation measured apoptosis. In addition, AGS cells received no pretreatment or preincubation for 1 h with 50-100 microM z-VAD, a pan-caspase inhibitor, and were then treated with 1-2 mM H(2)O(2). With high concentrations of H(2)O(2), cell death was predominantly necrotic, whereas lower concentrations evoked time and concentration dependent apoptosis. Furthermore, z-VAD pretreatment prevented oxidant induced apoptosis and necrosis. Since caspase cascade blockade prevents both processes, our results support the hypothesis that H(2)O(2) induced cell death is predominantly a caspase-mediated apoptosis.

Assessment of iron oxide nanoparticle ecotoxicity on regeneration and homeostasis in the replacement model system Schmidtea mediterranea_suppl

“…The generation of ROS is a known consequence of exposure to iron (Baker et al, 1997;Li et al, 2009) and has been described as a major effector of the toxicity of metal NPs, as it triggers inflammation, genotoxicity, fibrosis, and cancer (Dayem et al, 2017;Shvedova et al, 2012). Oxidative stress is also a crucial contributor to the toxicity of environmental toxicants (Leung et al, 2008). Since we found no effects of IONs on cell viability, regardless of the concentration used (Fig.…”

Scarless Fetal Mouse Wound Healing May Initiate Apoptosis Through Caspase 7 and Cleavage of PARP

“…As cells undergo these changes, endonucleases cleave the cells double stranded DNA. However, nucleosomal DNA, which is complexed with the core histones H2A, H2B, H3, and H4, is protected from endonuclease cleavage [12][13][14]. As the process progresses, cytoplasmic proteins become cross-linked, which causes cell shrinkage and may lead to formation of apoptotic bodies.…”

“…In early stages of this type of programmed cell death, endogenous endonucleases cleave the cellular double stranded DNA at the most accessible internucleosomal linker regions, which generate mono-and oligonucleosomes. This is in contrast to the DNA of the nucleosomes, which is complexed with the core histones H2A, H2B, H3, and H4, and is therefore protected from endonuclease cleavage [12][13][14]. The cell death detection ELISA assay evaluates samples for these histone-associated DNA fragments.…”

Benzo(a)pyrene-7,8-diol-9,10-epoxide induced p53-independent necrosis via the mitochondria-associated pathway involving Bax and Bak activation

“…15 Apoptosis and necrosis can occur concurrently and share some common pathways, which may be differentially induced by variable doses of pollutants. 16,17 However, the underlying molecular mechanisms still remain elusive.…”