Reactive oxygen intermediates as mediators of programmed cell death in plants and animals

Jabs, Thorsten

doi:10.1016/s0006-2952(98)00227-5

Cited by 539 publications

(323 citation statements)

References 153 publications

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“…AM-36 [1-(2-(4-chlorophenyl)-2-hydroxy)ethyl-4-(3,5-bis(1,1-dimethyl)-4-hydroxyphenyl)methylpiperazine] was designed and synthesized as described (Jarrott et al, 1997;1999). Neurobasal TM medium, TdT, B27 and N2 supplements were purchased from GibcoBRL Life technologies (Melbourne, Australia).…”

Section: Methodsmentioning

confidence: 99%

“…However, ROS have been shown to mediate neuronal death caused by a range of other cytotoxic agents in cultured cells including glutamate (Dawson et al, 1991;Tan et al, 1998), kainic acid (Sun et al, 1998), dopamine (O en et al, 1996), and serum deprivation (Satoh et al, 1996). In addition, a large body of experimental evidence implicates the involvement of ROS in apoptosis (Bonfoco et al, 1995;Jabs, 1999;McGowan et al, 1998;Sloviter et al, 1996;Sun et al, 1998). Antioxidants inhibit apoptotic cell death induced by a variety of di erent agents.…”

Section: A B C D E Fmentioning

confidence: 99%

“…ROS have been suggested to play a central role in the induction of apoptosis following exposure to a range of cytotoxic insults (Dirnagl et al, 1999;Jabs, 1999;Leist et al, 1998;Stoian et al, 1996). Apoptosis is induced by exposure to ROS in a variety of cell types (Bonfoco et al, 1995;Hanson et al, 1996;Hockenbery et al, 1993;Jacobson et al, 1995;McGowan et al, 1998;Stoian et al, 1996), is associated with oxidative stress induced by diverse cytotoxic insults (Devitt et al, 1999;Jabs, 1999;Leist et al, 1998) and is inhibited by antioxidants both in vitro and in vivo (Devitt et al, 1999;Hirose et al, 1993;Malorni et al, 1993;Melchiorri et al, 1998;Slater et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…AM-36 is a novel arylalkylpiperazine with combined antioxidant and Na + channel blocking activity within the one compound (Jarrott et al, 1997;1999). The activity of AM-36 has been tested in in vitro assays where it was found to inhibit lipid peroxidation in the thiobarbituric acid reacting substances assay with activity (IC 50 48 (39 ± 64) mM, 95% CI in parentheses) comparable to that of known antioxidants such as 3,5 tert-butyl-4-hydroxytoluene (BHT), U74500A and U83836E (Callaway et al, 1998;Jarrott et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM‐36, results in profound inhibition of neuronal apoptosis

Callaway¹,

Beart²,

Jarrott³

et al. 2001

British J Pharmacology

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1 AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na + channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to Na + channel activation, together with increased reactive oxygen species (ROS) production, are thought to contribute to neuronal death. Since neuronal death in the penumbra of the ischaemic lesion is suggested to occur by apoptosis, we investigated the ability of AM-36, antioxidants and Na + channel antagonists to inhibit toxicity induced by the neurotoxin, veratridine in cultured cerebellar granule cells (CGC's). 2 Veratridine (10 ± 300 mM) concentration-dependently reduced cell viability of cultured CGC's. Under the experimental conditions employed, cell death induced by veratridine (100 mM) possessed the characteristics of apoptosis as assessed by morphology, TUNEL staining and DNA laddering on agarose gels. 3 Neurotoxicity and apoptosis induced by veratridine (100 mM) were inhibited to a maximum of 50% by the antioxidants, U74500A (0.1 ± 10 mM) and U83836E (0.03 ± 10 mM), and to a maximum of 30% by the Na + channel blocker, dibucaine (0.1 ± 100 mM). In contrast, AM-36 (0.01 ± 10 mM) completely inhibited veratridine-induced toxicity ( IC 50 1.7 (1.5 ± 1.9) mM, 95% con®dence intervals (CI) in parentheses) and concentration-dependently inhibited apoptosis. 4 These ®ndings suggest veratridine-induced toxicity and apoptosis are partially mediated by generation of ROS. AM-36, which combines both Na + channel blocking and antioxidant activity, provided superior neuroprotection compared with agents possessing only one of these actions. This bifunctional pro®le of activity may underlie the potent neuroprotective e ects of AM-36 recently found in a stroke model in conscious rats.

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Section: Methodsmentioning

confidence: 99%

Section: A B C D E Fmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM‐36, results in profound inhibition of neuronal apoptosis

Callaway¹,

Beart²,

Jarrott³

et al. 2001

British J Pharmacology

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show abstract

“…The perturbation of mitochondrial function during the early stages of apoptosis is associated with an increased generation of reactive oxygen species (ROS) (Jabs, 1999), which creates an oxidative environment that contributes to the death process, at least in part, by resulting in the depletion of cellular antioxidants such as reduced glutathione (GSH) and by inducing direct damage to DNA, proteins, and lipids. Exogenous antioxidants, such as N-acetyl cysteine (NAC) and GSH, have thus been shown to protect cells against apoptosis (Hour et al, 1999;Shrivastava & Aggarwal, 1999;Li et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Protection by antioxidants against toxicity and apoptosis induced by the sulphur mustard analog 2‐chloroethylethyl sulphide (CEES) in Jurkat T cells and normal human lymphocytes

Han

Espinoza

Liao

et al. 2004

British J Pharmacology

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1 The mechanism of toxicity of sulphur mustard was investigated by examining the biochemical effects of the analog 2-chloroethylethyl sulphide (CEES) in both human Jurkat cells as well as normal human lymphocytes. 2 Exposure of both types of cells to CEES resulted in a marked decrease in the intracellular concentration of the reduced form of glutathione (GSH), and CEES-induced cell death was potentiated by L-buthionine sulphoximine, an inhibitor of GSH synthesis. 3 CEES increased the endogenous production of reactive oxygen species (ROS) in Jurkat cells, and CEES-induced cell death was potentiated by hydrogen peroxide. 4 CEES induced various hallmarks of apoptosis, including collapse of the mitochondrial membrane potential, proteolytic processing and activation of procaspase-3, and cleavage of poly (ADP-ribose) polymerase. 5 The effects of CEES on the accumulation of ROS, the intracellular concentration of GSH, the mitochondrial membrane potential, and caspase-3 activity were all inhibited by pretreatment of cells with the GSH precursor N-acetyl cysteine or with GSH-ethyl ester. Furthermore, CEES-induced cell death was also prevented by these antioxidants. 6 CEES toxicity appears to be mediated, at least in part, by the generation of ROS and consequent depletion of GSH. Given that sulphur mustard is still a potential biohazard, the protective effects of antioxidants against CEES toxicity demonstrated in Jurkat cells and normal human lymphocytes may provide the basis for the development of a therapeutic strategy to counteract exposure to this chemical weapon.

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Mitochondrial Perturbations and Oxidant Stress in Lymphocytes From Patients Undergoing Surgery and General Anesthesia

Delogu

Moretti²,

Famularo³

et al. 2001

Arch Surg

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Reactive oxygen intermediates as mediators of programmed cell death in plants and animals

Cited by 539 publications

References 153 publications

Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM‐36, results in profound inhibition of neuronal apoptosis

Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM‐36, results in profound inhibition of neuronal apoptosis

Protection by antioxidants against toxicity and apoptosis induced by the sulphur mustard analog 2‐chloroethylethyl sulphide (CEES) in Jurkat T cells and normal human lymphocytes

Mitochondrial Perturbations and Oxidant Stress in Lymphocytes From Patients Undergoing Surgery and General Anesthesia

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