Role of NADPH oxidase in the apoptotic death of cultured cerebellar granule neurons

Coyoy-Salgado, Angélica; Valencia, Antonio; Guemez‐Gamboa, Alicia; Morán, Julio

doi:10.1016/j.freeradbiomed.2008.06.027

Cited by 48 publications

(61 citation statements)

References 67 publications

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“…Significantly different from K25 (**), K5 (*), or ST wt (1) at P < 0.05. posed to play a central role in the initiation and execution of neuronal apoptosis (Schulz et al, 1996;Atlante et al, 1998;Valencia and Morán, 2001), there is a lack of information about the precise mechanism of action of ROS and their source during the apoptotic event. We recently demonstrated an active role of an NADPH oxidase in the apoptotic death of rat CGN induced by two different conditions (Coyoy et al, 2008). Here, we suggest that NADPH oxidase has an important role in apoptotic death of CGN, but the NOX homologue involved in it will depend on the condition used to induce apoptosis.…”

Section: Nox1 and Nox4 Are Expressed In Mouse Cgnmentioning

confidence: 69%

“…We have previously shown that different homologues of NOX2 are expressed in rat CGN (Coyoy et al, 2008). We therefore examined the expression of NOX1 and NOX4 in CGN from mouse, which has not been reported, and evaluated a possible difference in NOX1 and NOX4 expression between wt and ko CGN.…”

Section: Nox1 and Nox4 Are Expressed In Mouse Cgnmentioning

confidence: 96%

“…However, the source of ROS implicated in this model has not yet been identified. It has been proposed that NADPH oxidase could be responsible for the production of ROS involved in apoptotic cell death of cortical cells (Hwang et al, 2002;Kim et al, 2002), embryonic striatal cells (Ma and Zhou, 2006), and cerebellar granule neurons (Coyoy et al, 2008) as well as in a gerbil global cerebral ischemia model (Wang et al, 2006). In mice lacking NOX2, animals exhibited a higher resistance to neuronal loss after ischemia than wild-type mice (Walder, 1997).…”

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confidence: 99%

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NOX2 mediates apoptotic death induced by staurosporine but not by potassium deprivation in cerebellar granule neurons

Guemez‐Gamboa

Morán

2009

J of Neuroscience Research

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Neuronal apoptotic death involves the participation of reactive oxygen species (ROS), but their sources have not been completely elucidated. Previous studies have demonstrated that the ROS-producing enzyme NADPH oxidase is present in neuronal cells and that this enzyme could participate in the apoptotic neuronal death. Cerebellar granule neurons (CGN) undergo apoptosis when cells are transferred from a medium with 25 mM KCl (K25) to a 5 mM KCl (K5) medium or when they are treated with staurosporine (ST). Under these conditions, apoptotic death of CGN is dependent on ROS production. In this study, we evaluated the role of NOX2, an NADPH oxidase homolog, in the apoptotic death of CGN induced by two different conditions. In CGN from NOX2-deficient (ko) mice, a significantly lower rate of apoptotic death occurs compared with wild-type (wt) CGN. Also, caspase-3 activation, NADPH oxidase activity, and superoxide anion production induced by ST were markedly lower in ko neurons than in wt CGN. In contrast to the case with ST, when CGN were treated with K5, no differences were observed between ko and wt cells in any of the parameters measured. However, all NADPH oxidase inhibitors tested noticeably reduced cell death and apoptotic parameters induced by K5 in both wt and ko CGN. These results suggest that NOX2 could be necessary for apoptotic death induced by ST, but not by K5, which could require other member of the NOX family in the apoptotic process.

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Section: Nox1 and Nox4 Are Expressed In Mouse Cgnmentioning

confidence: 69%

Section: Nox1 and Nox4 Are Expressed In Mouse Cgnmentioning

confidence: 96%

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confidence: 99%

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NOX2 mediates apoptotic death induced by staurosporine but not by potassium deprivation in cerebellar granule neurons

Guemez‐Gamboa

Morán

2009

J of Neuroscience Research

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“…Very little is known regarding the function of Nox1 in the CNS. A recent study showed the involvement of NADPH oxidase-generated ROS in the apoptotic death of cerebellar granule neurons and speculated a role for Nox1 in this process (19). Moreover, Jackman et al investigated whether Nox1 is essential for superoxide production in large cerebral arteries in response to angiotensin II after ischemic stroke (32).…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase 1, a Novel Molecular Source of ROS in Hippocampal Neuronal Death in Vascular Dementia

Choi

Lee

Kim

et al. 2014

Antioxidants & Redox Signaling

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Aims: Chronic cerebral hypoperfusion (CCH) is a common pathological factor that contributes to neurodegenerative diseases such as vascular dementia (VaD). Although oxidative stress has been strongly implicated in the pathogenesis of VaD, the molecular mechanism underlying the selective vulnerability of hippocampal neurons to oxidative damage remains unknown. We assessed whether the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) complex, a specialized superoxide generation system, plays a role in VaD by permanent ligation of bilateral common carotid arteries in rats. Results: Male Wistar rats (10 weeks of age) were subjected to bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]). Nox1 expression gradually increased in hippocampal neurons, starting at 1 week after 2VO and for approximately 15 weeks after 2VO. The levels of superoxide, DNA oxidation, and neuronal death in the CA1 subfield of the hippocampus, as well as consequential cognitive impairment, were increased in 2VO rats. Both inhibition of Nox by apocynin, a putative Nox inhibitor, and adeno-associated virus-mediated Nox1 knockdown significantly reduced 2VO-induced reactive oxygen species generation, oxidative DNA damage, hippocampal neuronal degeneration, and cognitive impairment. Innovation and Conclusion: We provided evidence that neuronal Nox1 is activated in the hippocampus under CCH, causing oxidative stress and consequential hippocampal neuronal death and cognitive impairment. This evidence implies that Nox1-mediated oxidative stress plays an important role in neuronal cell death and cognitive dysfunction in VaD. Nox1 may serve as a potential therapeutic target for VaD. Antioxid. Redox Signal. 21, 533-550.

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“…Nox1, Nox2, and Nox4 are also contained in neurons. While investigating the role of NADPH oxidases in apoptotic death of cerebellar granule neurons of rats, Coyoy et al (39) reported protein expression of p22 phox , Nox1, Nox2, and Nox4 and the cytosolic p47 phox and p67 phox . At the mRNA level, also the expression of p40phox was detected.…”

Section: Nox Function In the Brainmentioning

confidence: 99%

Which NADPH Oxidase Isoform Is Relevant for Ischemic Stroke? The Case for Nox 2

Kahles

Brandes²

2013

Antioxidants & Redox Signaling

108

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Significance and Recent Advances: Ischemic stroke is the leading cause of disability and third in mortality in industrialized nations. Immediate restoration of cerebral blood flow is crucial to salvage brain tissue, but only few patients are eligible for recanalization therapy. Thus, the need for alternative neuroprotective strategies is huge, and antioxidant interventions have long been studied in this context. Reactive oxygen species (ROS) physiologically serve as signaling molecules, but excessive amounts of ROS, as generated during ischemia/ reperfusion (I/R), contribute to tissue injury. Critical Issues: Nevertheless and despite a strong rational of ROS being a pharmacological target, all antioxidant interventions failed to improve functional outcome in human clinical trials. Antioxidants may interfere with physiological functions of ROS or do not reach the crucial target structures of ROS-induced injury effectively. Future Directions: Thus, a potentially more promising approach is the inhibition of the source of disease-promoting ROS. Within recent years, NADPH oxidases (Nox) of the Nox family have been identified as mediators of neuronal pathology. As, however, several Nox homologs are expressed in neuronal tissue, and as many of the pharmacological inhibitors employed are rather unspecific, the concept of Nox as mediators of brain damage is far from being settled. In this review, we will discuss the contribution of Nox homologs to I/R injury at large as well as to neuronal damage in particular. We will illustrate that the current data provide evidence for Nox2 as the most important NADPH oxidase mediating cerebral injury.

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Role of NADPH oxidase in the apoptotic death of cultured cerebellar granule neurons

Cited by 48 publications

References 67 publications

NOX2 mediates apoptotic death induced by staurosporine but not by potassium deprivation in cerebellar granule neurons

NOX2 mediates apoptotic death induced by staurosporine but not by potassium deprivation in cerebellar granule neurons

NADPH Oxidase 1, a Novel Molecular Source of ROS in Hippocampal Neuronal Death in Vascular Dementia

Which NADPH Oxidase Isoform Is Relevant for Ischemic Stroke? The Case for Nox 2

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