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Title:
Caspase-2 activation in neural stem cells undergoing oxidative stress-induced apoptosis | Apoptosis
Description:
Oxidative stress occurs as a consequence of disturbance in the balance between the generation of reactive oxygen species (ROS) and the antioxidant defence mechanisms. The interaction of ROS with DNA can cause single-, or double-strand breaks that subsequently can lead to the activation of p53, which is central for the regulation of cellular response, e.g. apoptosis, to a range of environmental and intracellular stresses. Previous reports have suggested a regulatory role of p53 in the early activation of caspase-2, upstream of mitochondrial apoptotic signaling. Here we show that excessive ROS formation, induced by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) exposure, induces apoptosis in primary cultured neural stem cells (NSCs) from cortices of E15 rat embryos. Following DMNQ exposure cells exhibited apoptotic hallmarks such as Bax oligomerization and activation, cytochrome c release, caspase activation and chromatin condensation. Additionally, we could show early p53 accumulation and a subsequent activation of caspase-2. The attenuation of caspase-2 activity with selective inhibitors could antagonize the mitochondrial signaling pathway and cell death. Overall, our results strongly suggest that DMNQ-induced oxidative stress causes p53 accumulation and consequently caspase-2 activation, which in turn initiates apoptotic cell death via the mitochondria-mediated caspase-dependent pathway in NSCs.
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Keywords {๐}
google, scholar, pubmed, cas, article, cell, apoptosis, caspase, cells, death, oxidative, biol, activation, stress, neural, zhivotovsky, dna, stem, cancer, orrenius, res, cellular, bax, damage, biochem, nature, tamm, response, activity, sci, privacy, cookies, content, research, ceccatelli, oxygen, regulation, mitochondrial, apoptotic, signaling, induces, rat, access, usa, protein, mouse, chem, mol, induction, publish,
Topics {โ๏ธ}
spin-trapping compound n-tert-butyl-alpha-phenylnitrone month download article/chapter mitochondria-mediated caspase-dependent pathway dmnq-induced oxidative stress seizure-induced neuronal death neural stem cells n-cor controls differentiation boris zhivotovskyย &ย sandra ceccatelli serum-free supplemented medium hydrogen peroxide-induced apoptosis stress-induced apoptosis reactive oxygen species article apoptosis aims full article pdf multipotent neural precursors dna damaging agents tumor-suppressor protein p53 thymocyte apoptosis induced etoposide-induced apoptosis privacy choices/manage cookies related subjects age-related increase swedish research council stem cells dugich-djordjevic mm mitochondrial apoptotic signaling death receptor pathways nontransformed mouse cells superoxide ion-radical cancer cell apoptosis uva-induced cytotoxicity dna damage induces e15 rat embryos free amino acids oxidative stress lipid peroxidation products tumor-suppressor p53 tumor suppressor p53 cell death mouse nedd2 gene calcium-apoptosis link postnatal rat brain post-translational regulation caspase-2 induces apoptosis article tamm mitochondrial signaling pathway neuronal cells adult mouse neocortex cellular stress antioxidant defence mechanisms
Questions {โ}
- Betteridge DJ (2000) What is oxidative stress?
- Fadeel B, Orrenius S, Zhivotovsky B (1999) Apoptosis in human disease: a new skin for the old ceremony?
- Lu X, Lane DP (1993) Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes?
- Schwartz LM, Smith SW, Jones ME, Osborne BA (1993) Do all programmed cell deaths occur via apoptosis?
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headline:Caspase-2 activation in neural stem cells undergoing oxidative stress-induced apoptosis
description:Oxidative stress occurs as a consequence of disturbance in the balance between the generation of reactive oxygen species (ROS) and the antioxidant defence mechanisms. The interaction of ROS with DNA can cause single-, or double-strand breaks that subsequently can lead to the activation of p53, which is central for the regulation of cellular response, e.g. apoptosis, to a range of environmental and intracellular stresses. Previous reports have suggested a regulatory role of p53 in the early activation of caspase-2, upstream of mitochondrial apoptotic signaling. Here we show that excessive ROS formation, induced by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) exposure, induces apoptosis in primary cultured neural stem cells (NSCs) from cortices of E15 rat embryos. Following DMNQ exposure cells exhibited apoptotic hallmarks such as Bax oligomerization and activation, cytochrome c release, caspase activation and chromatin condensation. Additionally, we could show early p53 accumulation and a subsequent activation of caspase-2. The attenuation of caspase-2 activity with selective inhibitors could antagonize the mitochondrial signaling pathway and cell death. Overall, our results strongly suggest that DMNQ-induced oxidative stress causes p53 accumulation and consequently caspase-2 activation, which in turn initiates apoptotic cell death via the mitochondria-mediated caspase-dependent pathway in NSCs.
datePublished:2008-01-05T00:00:00Z
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description:Oxidative stress occurs as a consequence of disturbance in the balance between the generation of reactive oxygen species (ROS) and the antioxidant defence mechanisms. The interaction of ROS with DNA can cause single-, or double-strand breaks that subsequently can lead to the activation of p53, which is central for the regulation of cellular response, e.g. apoptosis, to a range of environmental and intracellular stresses. Previous reports have suggested a regulatory role of p53 in the early activation of caspase-2, upstream of mitochondrial apoptotic signaling. Here we show that excessive ROS formation, induced by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) exposure, induces apoptosis in primary cultured neural stem cells (NSCs) from cortices of E15 rat embryos. Following DMNQ exposure cells exhibited apoptotic hallmarks such as Bax oligomerization and activation, cytochrome c release, caspase activation and chromatin condensation. Additionally, we could show early p53 accumulation and a subsequent activation of caspase-2. The attenuation of caspase-2 activity with selective inhibitors could antagonize the mitochondrial signaling pathway and cell death. Overall, our results strongly suggest that DMNQ-induced oxidative stress causes p53 accumulation and consequently caspase-2 activation, which in turn initiates apoptotic cell death via the mitochondria-mediated caspase-dependent pathway in NSCs.
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