Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-κB

Dumont, Andreas; Hehner, Steffen P.; Hofmann, Thomas G.; Ueffing, Marius; Dröge, Wulf; Schmitz, M. Lienhard

doi:10.1038/sj.onc.1202325

Cited by 301 publications

(195 citation statements)

References 64 publications

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“…[52][53][54] These effects are due to opening of the pore complex on the mitochondrial membrane, which in normal circumstances shows a close conformation. The changes of the mitochondrial structure induce several functional alterations (collapse of the mitochondrial inner membrane potential, uncoupling of the respiratory chain, overproduction of ROS, release of ions and proteins), leading to apoptosis or necrosis.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Calcabrini¹,

Arancia²,

Marra³

et al. 2002

Intl Journal of Cancer

122

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The occurrence of resistance to cytotoxic agents in tumor cells, associated with several phenotypic alterations, is one of the major obstacles to successful anticancer chemotherapy. A new strategy to overcome MDR of human cancer cells was studied, using BSAO, which generates cytotoxic products from spermine, H 2 O 2 and aldehyde(s). The involvement of these products in causing cytotoxicity was investigated in both drug-sensitive (LoVo WT) and drug-resistant (LoVo DX) colon adenocarcinoma cells. Evaluation of clonogenic cell survival showed that LoVo DX cells are more sensitive than LoVo WT cells. Fluorometric assay and treatments performed in the presence of catalase demonstrated that the cytotoxicity was due mainly to the presence of H 2 O 2 . Cytotoxicity was eliminated in the presence of both catalase and ALDH. Transmission electron microscopic observations showed more pronounced mitochondrial modifications in drug-resistant than in drug-sensitive cells. Mitochondrial functionality studies performed by flow cytometry after JC-1 labeling revealed basal hyperpolarization of the mitochondrial membrane in LoVo DX cells. After treatment with BSAO and spermine, earlier and higher mitochondrial membrane depolarization was found in LoVo DX cells than in drug-sensitive cells. In addition, higher basal ROS production in LoVo DX cells than in drug-sensitive cells was detected by flow-cytometric analysis, suggesting increased mitochondrial activity in drug-resistant cells. Our results support the hypothesis that mitochondrial functionality affects the sensitivity of cells to the cytotoxic enzymatic oxidation products of spermine, which might be promising anticancer agents, mainly against drug-resistant tumor cells.

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Section: Discussionmentioning

confidence: 99%

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Calcabrini¹,

Arancia²,

Marra³

et al. 2002

Intl Journal of Cancer

122

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“…This transcription factor plays a dual role in apoptosis as a signal-dependent antagonist or promoter of cell death (Baichwal and Baeuerle, 1997). NF-kB activation protects from some apoptotic stimuli such as TNF-a, but is required for other cell death inducers such as H 2 O 2 and a-CD3 triggering (Dumont et al, 1999;Hettmann et al, 1999). Therefore, the inactivation of Vav1 may either antagonize apoptotic processes requiring NF-kB activation or promote apoptosis in a situation were NF-kB has a protective function.…”

Section: Discussionmentioning

confidence: 99%

Caspase-dependent cleavage and inactivation of the Vav1 proto-oncogene product during apoptosis prevents IL-2 transcription

et al. 2000

Self Cite

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“…Studies indicated that mitochondria is the source of cytochrome c release and ROS generation in mammal cells [79]. Dumont et al reported that H 2 O 2 induces the release of mitochondria cytochrome c and ROS in human T-cells [37]. Interestingly, zVAD-fmk reduced the • OH-induced cytochrome c release and ROS generation in carp erythrocytes.…”

Section: • Oh-induced Apoptosis In Fish Erythrocytesmentioning

confidence: 99%

“…CD95) with subsequent caspase-8 activation, and stimulate the release of mitochondrial cytochrome c with subsequent caspase-9 activation [35], both caspases converge finally at the activation of effector caspases (e.g. caspase-3) that results in nucleus DNA fragmentation (a biomarker of apoptosis) in mammal nucleated cells [36][37][38]. It has been reported that the mechanisms of antioxidant defences in fish cells are similar to those in mammal nucleated cells [39][40][41].…”

Section: Introductionmentioning

confidence: 99%

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Jiang

Liu

et al. 2016

Free Radical Biology and Medicine

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a b s t r a c tThe present study explored the apoptosis pathways in hydroxyl radicals ( • OH)-induced carp erythrocytes. Carp erythrocytes were treated with the caspase inhibitors in physiological carp saline (PCS) or Ca 2 þ -free PCS in the presence of 40 μM FeSO 4 /20 μM H 2 O 2 . The results showed that the generation of reactive oxygen species (ROS), the release of cytochrome c and DNA fragmentation were caspase-dependent, and Ca 2 þ was involved in calpain activation and phosphatidylserine (PS) exposure in • OH-induced carp erythrocytes. Moreover, the results suggested that caspases were involved in PS exposure, and Ca 2 þ was involved in DNA fragmentation in • OH-induced fish erythrocytes. These results demonstrated that there might be two apoptosis pathways in fish erythrocytes, one is the caspase and cytochrome c-dependent apoptosis that is similar to that in mammal nucleated cells, the other is the Ca 2 þ -involved apoptosis that was similar to that in mammal non-nucleated erythrocytes. So, fish erythrocytes may be used as a model for studying oxidative stress and apoptosis in mammal cells. Furthermore, the present study investigated the effects of glutamine (Gln)'s metabolites [alanine (Ala), citrulline (Cit), proline (Pro) and their combination (Ala 10 Pro 4 Cit 1 )] on the pathways of apoptosis in fish erythrocytes. The results displayed that Ala, Cit, Pro and Ala 10 Pro 4 Cit 1 effectively suppressed ROS generation, cytochrome c release, activation of caspase-3, caspase-8 and caspase-9 at the physiological concentrations, prevented Ca 2 þ influx, calpain activation, PS exposure, DNA fragmentation and the degradation of the cytoskeleton and oxidation of membrane and hemoglobin (Hb) and increased activity of anti-hydroxyl radical (AHR) in • OH-induced carp erythrocytes. Ala 10 Pro 4 Cit 1 produced a synergistic effect of inhibited oxidative stress and apoptosis in fish erythrocytes. These results demonstrated that Ala, Cit, Pro and their combination can protect mammal erythrocytes and nucleated cells against oxidative stress and apoptosis. The studies supported the use of Gln, Ala, Cit and Pro as oxidative stress and apoptosis inhibitors in mammal cells and the hypothesis that the inhibited effects of Gln on oxidative stress and apoptosis are at least partly dependent on that of its metabolites in mammalian.

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Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-κB

Cited by 301 publications

References 64 publications

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Caspase-dependent cleavage and inactivation of the Vav1 proto-oncogene product during apoptosis prevents IL-2 transcription

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

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