Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

Korystov, Yuri N.; Dobrovinskaya, Oxana; Shaposhnikova, V. V.; Eidus, L.Kh.

doi:10.1016/0014-5793(96)00538-8

Cited by 32 publications

(21 citation statements)

References 30 publications

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“…Moreover, overexpression of superoxide dismutase, which leads to formation of H 2 O 2 , is associated with impaired LTP in CA1 in vitro, and LTP is restored in slices prepared from these transgenic mice by addition of catalase (40), which metabolizes H 2 O 2 to O 2 and H 2 O. The mechanism by which irradiation leads to an increase in ROS is not known; however, it has been shown that exposure of thymocytes to irradiation leads to metabolism of arachidonic acid by lipoxygenase (41), and this action can lead to the generation of ROS. It has also been reported that irradiation increases generation of eicosanoids (42) including prostaglandin E 2 (42,43), which is produced by the action of cyclooxygenase on arachidonic acid.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

Lonergan¹,

Martin²,

Horrobin³

et al. 2002

Journal of Biological Chemistry

112

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Exposure to irradiation leads to detrimental changes in several cell types. In this study we assessed the changes induced in hippocampus by exposure of rats to whole body irradiation; the findings reveal that irradiation leads to apoptotic cell death in hippocampus, and as a consequence, long term potentiation in perforant path-granule cell synapses is markedly impaired. The evidence is consistent with the view that irradiation induced an increase in reactive oxygen species and that this leads to stimulation of the stress-activated protein kinase, JNK, and activation of the transcription factor, c-Jun. Consequent upon activation of JNK, a cascade of cell signaling events was stimulated that ultimately resulted in apoptosis, as suggested by parallel increases in cytochrome c translocation, caspase-3 activation, poly-(ADP-ribose) polymerase cleavage, and terminal dUTP nick-end labeling staining. Treatment of rats with eicosapentaenoic acid inhibited the irradiation-induced increase in reactive oxygen species production and the subsequent cellular signaling events, suggesting that oxidative stress triggered apoptotic cell death in the hippocampus of rats exposed to irradiation. Significantly, when the compromise in cell viability induced by irradiation was prevented by eicosapentaenoic acid, long term potentiation was sustained in a manner similar to that in the sham-treated control group.

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Section: Resultsmentioning

confidence: 99%

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

Lonergan¹,

Martin²,

Horrobin³

et al. 2002

Journal of Biological Chemistry

112

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“…Some authors consider them anti-apoptotic (Hebert et al, 1996, Krajcsi et al, 1996, Tang et al, 1996, Koller et al, 1997, others, proapoptotic (Koller et al, 1997, Fisher et al, 1997. As to the proapoptotic effect of eicosanoids, cell treatments with inhibitors of lipoxygenase are cytoprotective in leukocytes (Korystov et al, 1996). As to the proapoptotic effect of eicosanoids, cell treatments with inhibitors of lipoxygenase are cytoprotective in leukocytes (Korystov et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis

Pompéia

Freitas

Kim

et al. 2002

Biology of the Cell

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Arachidonic acid (AA)-induced cytotoxicity was evaluated in leukocytes: the human leukemia cell lines HL-60, Jurkat and Raji and in rat lymphocytes. Such cytotoxicity was dose- and time-dependent. At concentrations below 5 microM, AA was not toxic; at 10-400 microM, AA induced apoptosis and at concentrations beyond 400 microM, necrosis. The minimum exposure time to trigger cell death was of around 1 h, but the effect was increased by longer exposure times until 6-24 h. Apoptosis was morphologically characterized by a decrease in cell and nuclear volume, chromatin condensation and DNA fragmentation and the presence of lipid bodies, without changes in organelle integrity. Biochemically, AA-induced apoptosis was associated with internucleosomal fragmentation and caspase activation, evaluated by PARP cleavage and the use of a caspase inhibitor. Necrosis was characterized by increased cell volume, presence of loose chromatin, appearance of vacuoles, loss of membrane integrity and of the definition of organelles. The apoptotic effect of AA was studied as to oxidative-reductive imbalance and the participation of eicosanoids. Apoptotic AA treatment was accompanied by an increase in the quantity of thiobarbituric acid reactive substances (TBARS), low-level chemiluminescence and in the glutathione disulfide/reduced glutathione ratio, indicating oxidative stress. The addition of tocopherol, ascorbate, prostaglandin E2 and lipoxygenase inhibitors delayed cell death, whereas the inhibition of cyclooxygenase promoted AA-induced cell death. Cell treatment with AA was accompanied by increased cellular production of LTB4. AA, therefore, is cytotoxic at physiological and supraphysiological concentrations, causing apoptosis and necrosis. Cell treatment with apoptotic concentrations of AA involves oxidative stress and changes in eicosanoid biosynthesis.

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“…The present study is the first to demonstrate the involvement of a signaling pathway consisting sequentially of activation of PLA 2 , generation of superoxide anion, and finally activation of NF-B in DEN-2 virus-induced apoptosis of human neuroblastoma cells. PLA 2 plays a key role in cellular signaling by generating a wide array of biologically active lipid mediators (31,40,82). PLA 2 -mediated hydrolysis of phospholipids results in the release of AA, which may either exert direct effects or serve as a substrate for the generation of other lipid messengers, such as prostaglandins and leukotrienes (2).…”

Section: Discussionmentioning

confidence: 99%

“…Among the various types of PLA 2 , a cytosolic PLA 2 (cPLA 2 ) which preferentially cleaves sn-2-arachidonyl-containing phospholipids has been reported to be activated in response to a variety of stressors, such as tumor necrosis factor alpha (TNF-␣), FasL, and irradiation, and is essential for the induction of apoptosis (31,40,47,54,82). Malewicz et al reported that dengue virus was able to activate PLA 2 in BHK-21 cells and generate AA (50); however, the effect of AA on these cells was not assessed.…”

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confidence: 99%

Potential Dengue Virus-Triggered Apoptotic Pathway in Human Neuroblastoma Cells: Arachidonic Acid, Superoxide Anion, and NF-κB Are Sequentially Involved

Jan¹,

Chen

Ma³

et al. 2000

J Virol

116

100

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Direct in vivo evidence for the susceptibility of human neuronal cells to dengue virus has not been reported.In this study, we demonstrated that type 2 dengue (DEN-2) virus infection induced extensive apoptosis in the human neuroblastoma cell line SK-N-SH. Phospholipase A 2 (PLA 2 ) was activated by DEN-2 infection, which led to the generation of arachidonic acid (AA). Inhibition of PLA 2 activity by the PLA 2 inhibitors, AACOCF 3 and ONO-RS-082, diminished DEN-2 virus-induced apoptosis. In contrast, the cyclooxygenase inhibitors aspirin and indomethacin, thought to increase AA accumulation by blocking AA catabolism, enhanced apoptosis. Exogenous AA induced apoptosis in a dose-dependent manner. Superoxide anion, which is thought to be generated through the AA-activated NADPH oxidase, was increased after infection. Pretreatment with superoxide dismutase (SOD) protected cells against DEN-2 virus-induced apoptosis. Furthermore, generation of superoxide anion was blocked by AACOCF 3 . In addition, the transcription factors, NF-B and c-Jun, were found to be activated after DEN-2 virus infection. However, pretreatment of cells with oligodeoxynucleotides containing NF-B, but not c-Jun, binding sites (transcription factor decoy) strongly prevented dengue virusinduced apoptosis. The finding that AACOCF 3 and SOD significantly block activation of NF-B suggests that this activation is derived from the AA-superoxide anion pathway. Our results indicate that DEN-2 virus infection of human neuroblastoma cells triggers an apoptotic pathway through PLA 2 activation to superoxide anion generation and subsequently to NF-B activation. This apoptotic effect can be either directly derived from the action of AA and superoxide anion on mitochondria or indirectly derived from the products of apoptosis-related genes activated by NF-B.Dengue virus, a mosquito-borne human pathogen, is a member of the Flaviviridae and is classified into four serotypes (Dengue virus type 1 through 4, designated here DEN-1, -2, -3, and -4 virus) (27,74). Dengue disease, which is caused by dengue virus infection, is considered a major public health problem in Southeast Asia and Central America (25, 58). As a consequence of increasing travel to areas of endemicity, dengue infection has been imported to many parts of the world. Classic dengue fever generally presents in older children and adults with high fever, severe headache and retro-orbital pain, myalgia, arthralgia, nausea, and rash. The acute phase may last for up to a week, but prolonged recovery is common and is sometimes associated with fatigue and depression. In some cases, hemorrhagic manifestations (dengue hemorrhagic fever) and signs of circulatory failure occur, leading to sudden and often hypovolemic shock (dengue shock syndrome) (26,88). An increasing number of cases have been reported with manifestations of encephalopathy and encephalitis, which cover a wide range of symptoms and signs from headache and clouded sensorium to convulsion, spasticity, and coma (34,49,73,79). As a result, the etiolo...

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Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

Cited by 32 publications

References 30 publications

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis

Potential Dengue Virus-Triggered Apoptotic Pathway in Human Neuroblastoma Cells: Arachidonic Acid, Superoxide Anion, and NF-κB Are Sequentially Involved

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