Alteration of Bcl-2 expression in the nigrostriatal system after kainate injection with or without melatonin co-treatment

Chuang, Jih Ing; Chen, Shur-Tzu; Chang, Yung-Heng; Jen, L.S.

doi:10.1016/s0891-0618(01)00109-0

Cited by 14 publications

(12 citation statements)

References 46 publications

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“…These are the initial upregulation of the antiapoptotic factor Bcl-2 within the first 12 h, followed by a decline until 3 days following kainate treatment and a second peak thereafter. Thus, our data support the hypothesis of Bcl-2 upregulation following kainate exposure (Chuang et al 2001;Lopez et al 1999;Yalcin et al 2004), while we don't see an attenuation of Bcl-2 as it was described by others before (Gillardon et al 1995). The biphased Bcl-2 response to kainate exposure might depend on changing sensitivity of neurons as suggested above (Mori et al 2005;Zaczek et al 1980).…”

Section: Discussionsupporting

confidence: 89%

“…Administration of kainate leads to experimental epilepsy and is associated with an increase in cell death and modulation of factors influencing apoptosis. However, different mechanisms were suggested, depending on whether or not Bcl-2 expression is upregulated after kainate administration (Chuang et al 2001;Gillardon et al 1995;Hockenbery et al 1990;Yalcin et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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Transient Protective Effect of B-Vitamins in Experimental Epilepsy in the Mouse Brain

et al. 2009

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The regulation of programmed cell death in the nervous system of vertebrates is a complex mechanism aimed to remove superfluous or damaged cells. Epileptic seizures can lead to an activation of pathways resulting in neuronal cell death. B-vitamins might have a neuroprotective potential reducing cell death following appropriate stimulation. Here, the role of the B-vitamins B(1) (thiamine), B(6) (pyridoxine), and B(12) (cobalamine) was investigated in a mouse model of experimental epilepsy induced by kainate. B-vitamin pre-treated animals showed a significantly reduced epileptic score during the first 15 min after kainate injection. The molecular response to kainate showed a bi-phased time course with early induction of Bcl-2 expression within 12 h and a second induction after 7 days of kainate exposure. B-vitamin pre-treatment resulted in significant higher Bcl-2 expression in control animals (no kainate) and at 12 h within the early phase. Bcl-2 expression was not affected by B-vitamins within the second phase. BAX expression was not significantly influenced during the whole experiment. Three days after kainate stimulation, the number of TdT-mediated dUTP-biotin nick end labeling-positive cells in the hippocampal region was lower in B-vitamin-treated animals. Therefore, B-vitamin pre-treatment may attenuate the response to epileptic stimulation.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Transient Protective Effect of B-Vitamins in Experimental Epilepsy in the Mouse Brain

et al. 2009

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“…Other reports indicate that oxidative insults and GSH reduction in various neurodegenerative models can be effectively prevented by melatonin treatment (Chen and Chuang, 1999;Reiter et al, 2000;Chuang et al, 2001;Chen et al, 2002). Melatonin inhibits BSO-induced cataract formation in the newborn rat by reducing lipid peroxidation and the high ratio of GSSG/GSH (Abe et al, 1994;Li et al, 1997).…”

Section: Discussionmentioning

confidence: 97%

Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin

2003

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It is well known that intracellular antioxidant glutathione (GSH) plays major roles in the maintenance of redox status and defense of oxidative stress. Ras, a small GTPbinding protein, may send growth-stimulating message to the nucleus through downstream Rac oncoprotein and superoxide (O 2 À ). These findings led us to investigate the effects of GSH and melatonin, a free-radical scavenger, on Ras-Rac-O 2 À -related growth signal transduction. Our results demonstrate that overexpression of the inducible Ha-ras oncogene by isopropyl-b-d-thiogalactoside (IPTG) increases the levels of reactive oxygen species (ROS, including O 2 À and hydrogen peroxide (H 2 O 2 )) and GSH in an Ha-ras-transformed NIH/3T3 fibroblast cell line. On the contrary, melatonin significantly suppresses ras-triggered cell growth by inhibiting the increase of ROS and GSH. Moreover, severe apoptosis of this transformed cell line occurred when the cell redox balance between ROS and GSH was dramatically changed in the presence of IPTG and l-buthionine-[S,R]-sulfoximine (BSO, a specific inhibitor of GSH synthetase). That BSO-induced cell apoptosis needs Ras to increase the ROS level was demonstrated by the free-radical scavenger melatonin. It effectively blocked cell apoptosis, but cell growth was also slowed without affecting Ras expression. Based on our studies, two approaches can be applied to treating ras-related cancers. One is utilizing melatonin to suppress cancer cell proliferation, and the other is utilizing BSO to induce cancer-cell apoptosis. Cotreatment of rasrelated cancer cells with melatonin and BSO stops cell growth as well as apoptosis. Whether these cancer cells will undergo further regression or become recurrent merits investigation.

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“…Chuang and co-workers [49] provided direct evidence that in fact apoptosis was the process that leads to cellular implosion after kainate is given. Three days following the intrastriatal injection of kainic acid, these workers noted the dramatic cytotoxic action of the drug along with elevated Bcl-2 immunoreactivity in TUNEL-positive cells.…”

Section: Kainic Acidmentioning

confidence: 99%

Neurotoxins: Free Radical Mechanisms and Melatonin Protection

2010

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Toxins that pass through the blood-brain barrier put neurons and glia in peril. The damage inflicted is usually a consequence of the ability of these toxic agents to induce free radical generation within cells but especially at the level of the mitochondria. The elevated production of oxygen and nitrogen-based radicals and related non-radical products leads to the oxidation of essential macromolecules including lipids, proteins and DNA. The resultant damage is referred to as oxidative and nitrosative stress and, when the molecular destruction is sufficiently severe, it causes apoptosis or necrosis of neurons and glia. Loss of brain cells compromises the functions of the central nervous system expressed as motor, sensory and cognitive deficits and psychological alterations. In this survey we summarize the publications related to the following neurotoxins and the protective actions of melatonin: aminolevulinic acid, cyanide, domoic acid, kainic acid, metals, methamphetamine, polychlorinated biphenyls, rotenone, toluene and 6-hydroxydopamine. Given the potent direct free radical scavenging activities of melatonin and its metabolites, their ability to indirectly stimulate antioxidative enzymes and their efficacy in reducing electron leakage from mitochondria, it would be expected that these molecules would protect the brain from oxidative and nitrosative molecular mutilation. The studies summarized in this review indicate that this is indeed the case, an action that is obviously assisted by the fact that melatonin readily crosses the blood brain barrier.

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Alteration of Bcl-2 expression in the nigrostriatal system after kainate injection with or without melatonin co-treatment

Cited by 14 publications

References 46 publications

Transient Protective Effect of B-Vitamins in Experimental Epilepsy in the Mouse Brain

Transient Protective Effect of B-Vitamins in Experimental Epilepsy in the Mouse Brain

Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin

Neurotoxins: Free Radical Mechanisms and Melatonin Protection

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