Nitric Oxide Triggers the Toxicity due to Glutathione Depletion in Midbrain Cultures through 12-Lipoxygenase

Canals, Santiago; Casarejos, Marı́a José; Bernardo, Sonsoles de; Rodrı́guez-Martı́n, Eulalia; Mena, María A.

doi:10.1074/jbc.m213174200

Cited by 98 publications

(102 citation statements)

References 66 publications

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“…However, a possible influence of chronic NOS inhibition on apoptosis could modify the number of precursors ready to divide at the time of BrdU administration. Such a possibility is based on results obtained in cultured neurons, in which NO can either protect from (Ciani et al, 2002a,b) or induce apoptosis (Canals et al, 2001(Canals et al, , 2003, depending on the culture conditions. Our results demonstrate that the number of cells dying at any given time point after L-NAME administration was not significantly different from those present in control animals, therefore ruling out any effect of endogenous NO on programmed cell death in the adult SVZ-OB.…”

Section: Endogenous No Inhibited Cell Proliferation and Did Not Affecmentioning

confidence: 99%

Nitric Oxide Is a Physiological Inhibitor of Neurogenesis in the Adult Mouse Subventricular Zone and Olfactory Bulb

Moreno‐López¹,

Romero‐Grimaldi²,

Noval³

et al. 2004

J. Neurosci.

211

188

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The subventricular zone of the rodent brain retains the capacity of generating new neurons in adulthood. The newly formed neuroblasts migrate rostrally toward the olfactory bulb, where they differentiate as granular and periglomerular interneurons. The reported presence of differentiated neurons expressing the neuronal isoform of nitric oxide synthase (NOS) in the periphery of the neurogenic region and the organization of their varicose axons as a network in which the precursors are immersed raised the hypothesis that endogenous nitric oxide (NO) may participate in the control of neurogenesis in the subventricular zone. Systemic administration of the NOS inhibitors N -nitro-L-arginine methyl ester or 7-nitroindazole to adult mice produced a dose-and time-dependent increase in the number of mitotic cells in the subventricular zone, rostral migratory stream, and olfactory bulb, but not in the dentate gyrus of the hippocampus, without affecting apoptosis. In the subventricular zone, this effect was exerted selectively on a precursor subpopulation expressing nestin but not neuronal or glial cell-specific proteins. In addition, in the olfactory bulb, analysis of maturation markers in the newly generated neurons indicated that chronic NOS inhibition caused a delay in neuronal differentiation. Postmitotic cell survival and migration were not affected when NO production was impaired. Our results suggest that NO, produced by nitrergic neurons in the adult mouse subventricular zone and olfactory bulb, exerts a negative control on the size of the undifferentiated precursor pool and promotes neuronal differentiation.

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Section: Endogenous No Inhibited Cell Proliferation and Did Not Affecmentioning

confidence: 99%

Nitric Oxide Is a Physiological Inhibitor of Neurogenesis in the Adult Mouse Subventricular Zone and Olfactory Bulb

Moreno‐López¹,

Romero‐Grimaldi²,

Noval³

et al. 2004

J. Neurosci.

211

188

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“…In addition to producing 12(S)-and 15(S)-HETE, the enzyme is involved in the biosynthesis of lipoxins, hepoxilins, and other products. It is likely that 12/15-LOX-inhibiting or knockout mice are defi cient in a complex mixture of lipid mediators that have been proven to mediate both pro-and antiinfl ammatory pathways [for review see ( 78,79 ) (80)(81)(82)(83). Moreover, phospholipid glutathione peroxidase in the 12/15-LOX pathway is a GSH-dependent peroxidase ( 84 ).…”

Section: Discussionmentioning

confidence: 99%

“…HETEs is very rapid, GSH decrease is able to inhibit the reduction of endogenous HPETE to HETE ( 80,85 ). The increases in both HPETE half-life and its toxicity have been observed in neurons under GSH-depleted conditions ( 80,81 ).…”

Section: Downloaded Frommentioning

confidence: 99%

12/15-Lipoxygenase metabolites of arachidonic acid activate PPARγ: a possible neuroprotective effect in ischemic brain

Sun

Han

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org to form a series of biologically active lipid mediators ( 1, 2 ). In the CNS, 12/15-LOX expression has been described throughout the cerebrum, basal ganglia, and hippocampus ( 3, 4 ). Arachidonic acid (AA) is an important component of membrane lipids that can activate several signaling pathways directly by itself or by its metabolites ( 5 ). In nervous tissue, the major enzymatic route for AA metabolism is the 12/15-LOX pathway, and the principal metabolites are 12(S)-HETE and 15(S)-HETE ( 3, 4, 6, 7 ). The biological signifi cance of these metabolites of AA is that they have been proposed to play roles as second messengers in synaptic transmission and they are thought to be involved in learning and memory processes ( 8 ). In addition, 12(S)-HETE is known to act as an inhibitory neuromodulator by reducing voltage-sensitive calcium channel activity ( 9 ) and attenuating glutamate release and affi nity to its receptors ( 10-12 ).Brain ischemia triggers the massive release of free fatty acids from membrane stores, such as AA and DHA, and then the accumulation of lipid peroxides. 12/15-LOX is thought to be damaging because of its lipid-oxidizing properties, and the detrimental effects of 12/15-LOX have been documented by demonstrating the protection in the ischemic brain through 12/15-LOX inhibition or gene deletion ( 13-15 ). Several metabolites of 12/15-LOX, however, have neuroprotective and anti-infl ammatory qualities during brain ischemia. For example, 12/15-LOX metabolites derived from DHA and other -3 fatty acids inhibit cerebral ischemia-induced injury (16)(17)(18). This suggests 12/15-LOX and its metabolites may differ in their effects following cerebral ischemia.PPAR ␥ is a member of the nuclear hormone receptor family of ligand-dependent transcription factors. This work was supported by grants from the National Natural Science Foundation of China (number 81070968 to L.S. and number 81401023 to Y-W.X.) and from the Tianjin Municipal Science and Technology Commission (number 13ZCZDSY01900 to Y.C.). The authors declare no confl icts of interest. Manuscript received 15 July 2014 and in revised form 12(S)-and 15(S)-HETE activate PPAR ␥ in ischemic brain 503animals survived the MCAO surgical procedure. Rats that did not demonstrate neurological defi cits during 90 min MCAO were excluded from further study. Animals dying prematurely during the reperfusion period or having subarachnoid hemorrhage at postmortem examination were also excluded. Measurements derived from these animals were not included in the present study. Drug treatmentEicosanoids, 12(S)-HETE and 15(S)-HETE, were products of Cayman Chemical (Ann Arbor, MI) and given 30 min before the onset of MCAO by icv injection. 12(S)-and 15(S)-HETE, supplied in ethanol at 1 mg/ml, were air-dried under a stream of nitrogen and dissolved in a 30% DMSO and 70% isotonic saline solution ( 35 ). Animals received either vehicle (30% DMSO-0.9% saline) or a single dose of 12(S)-or 15(S)-HETE at 10, 15, or 20 g ( ‫...

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“…Highly reactive oxygen radicals are produced during the conversion of HPETEs to HETEs (74), contributing to the overall burden of oxidative stress following stroke. Under conditions of glutathione (GSH) depletion, as in acute focal stroke, 12-LOX derived 12-HPETE triggers nitric oxide (NO) induced neural cell death (24). Meanwhile, inhibitors of cPLA 2 and 12-LOX have been demonstrated to prevent neurotoxicity in vitro (84).…”

Section: Hydroperoxy-and Hydroxy-eicosatetraenoic Acidsmentioning

confidence: 99%

Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke

Rink

Khanna

2011

Antioxidants & Redox Signaling

168

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The significance of the hypoxia component of stroke injury is highlighted by hypermetabolic brain tissue enriched with arachidonic acid (AA), a 22:6n-3 polyunsaturated fatty acid. In an ischemic stroke environment in which cerebral blood flow is arrested, oxygen-starved brain tissue initiates the rapid cleavage of AA from the membrane phospholipid bilayer. Once free, AA undergoes both enzyme-independent and enzyme-mediated oxidative metabolism, resulting in the formation of number of biologically active metabolites which themselves contribute to pathological stroke outcomes. This review is intended to examine two divergent roles of molecular dioxygen in brain tissue as (1) a substrate for life-sustaining homeostatic metabolism of glucose and (2) a substrate for pathogenic metabolism of AA under conditions of stroke. Recent developments in research concerning supplemental oxygen therapy as an intervention to correct the hypoxic component of stroke injury are discussed. Antioxid. Redox Signal. 14, 1889-1903. Brain Oxygen Consumption and Regulation

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Nitric Oxide Triggers the Toxicity due to Glutathione Depletion in Midbrain Cultures through 12-Lipoxygenase

Cited by 98 publications

References 66 publications

Nitric Oxide Is a Physiological Inhibitor of Neurogenesis in the Adult Mouse Subventricular Zone and Olfactory Bulb

Nitric Oxide Is a Physiological Inhibitor of Neurogenesis in the Adult Mouse Subventricular Zone and Olfactory Bulb

12/15-Lipoxygenase metabolites of arachidonic acid activate PPARγ: a possible neuroprotective effect in ischemic brain

Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke

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