Nerve Growth Factor Protects against 6-Hydroxydopamine-induced Oxidative Stress by Increasing Expression of Heme Oxygenase-1 in a Phosphatidylinositol 3-Kinase-dependent Manner

Salinas, Marta; Díaz, Raquel; Abraham, Nader G.; Galarreta, C. M. Ruiz de; Cuadrado, Antonio

doi:10.1074/jbc.m209164200

Cited by 233 publications

(203 citation statements)

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“…3 and 4). The PI3K/Akt pathway was examined as an upstream signaling mechanism of Nrf2 activation, in view of several reports that this pathway is related to HO-1 expression (Martin et al, 2004;Salinas et al, 2003). For example, NGF and herb-derived phenol carnosol enhance HO-1 expression through PI3K/Akt activation in PC12 cells (Martin et al, 2004;Salinas et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Earlier studies show that the PI3K signaling pathway is involved in HO-1 expression (Salinas et al, 2003). Initially, we examined whether adenosine induces Akt phosphorylation, since PI3K phosphorylates Akt (Paez and Sellers, 2003).…”

Section: Adenosine Induces Ho-1 Expression Via Phosphatidylinositol 3mentioning

confidence: 99%

“…In response to diverse HO-1 inducers, Nrf2 translocates from the cytosol to the nucleus, and binds the antioxidant response element (ARE) in the promoter region of the HO-1 gene (Ishii et al, 2000). Additionally, phosphatidylinositol 3-kinase (PI3K) and its downstream signaling molecule, Akt, mediate HO-1 expression induced by NGF and hemin in PC12 and SH-SY5Y cells, respectively (Nakaso et al, 2003;Salinas et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Min

Kim

Jou

et al. 2008

Glia

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Adenosine, a purine nucleoside, has been reported to suppress the inflammatory responses of microglia in the brain. However, the underlying mechanisms of its anti-inflammatory action are unclear at present. Here we show that adenosine reduces the increase in intracellular reactive oxygen species (ROS) through expression of an antioxidant enzyme, hemeoxygenase-1 (HO-1). The H 2 O 2 -induced intracellular ROS level was significantly low in microglia pretreated with adenosine for 3-6 h, compared with that in untreated cells. Adenosine induced HO-1 mRNA and protein expression within 3 h, which was maintained for up to 12 h. Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, and phosphatidylinositol 3-kinase (PI3K) and Akt pathways appear to mediate HO-1 expression. In response to adenosine, Nrf2 translocated from the cytosol to nuclei, and bound to the antioxidant response element (ARE). Adenosine enhanced HO-1 promoter activity in an ARE-dependent manner. Moreover, the nucleoside stimulated Akt phosphorylation, and suppressors of PI3K (LY294002 and wortmannin) reduced adenosine-induced HO-1 expression. However, we propose that the effects of adenosine are independent of adenosine receptors, since agonists and antagonists of A1, A2a, and A3 had little effect on the regulation of intracellular ROS and HO-1 expression. Our results collectively suggest that adenosine acts as an endogenous regulator of brain inflammation via modulation of microglial ROS production. V

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Section: Discussionmentioning

confidence: 99%

Section: Adenosine Induces Ho-1 Expression Via Phosphatidylinositol 3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Min

Kim

Jou

et al. 2008

Glia

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“…Other investigators have shown that in vitro exposure to 6-OHDA increases oxidative stress and may lead to apoptosis (Kumar et al, 1995,Park et al, 2002,Soto-Otero et al, 2002,Holtz and O'Malley, 2003,Salinas et al, 2003,Ugarte et al, 2003,Zhuo et al, 2003,Datla et al, 2004,Elkon et al, 2004,Mazzio et al, 2004, and some elements of apoptosis and degeneration occur shortly after in vivo administration of 6-OHDA (Jeon et al, 1995,Joo et al, 1998,Zuch et al, 2000,Kramer and Mytilineou, 2004,Mladenovic et al, 2004. However, little has been reported on in vivo markers of oxidative stress after 6-OHDA administration.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson’s disease

Smith

Cass

2007

Neuroscience

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Although the etiology of Parkinson's disease (PD) is unknown, a common element of most theories is the involvement of oxidative stress, either as a cause or effect of the disease. There have been relatively few studies that have characterized oxidative stress in animal models of PD. In the present study a 6-hydroxydopamine (6-OHDA) rodent model of PD was used to investigate the in vivo production of oxidative stress after administration of the neurotoxin. 6-OHDA was injected into the striatum of young adult rats and the production of protein carbonyls and 4-hydroxynonenal (HNE) was measured at 1, 3, 7, and 14 days after administration. A significant increase in both markers was found in the striatum 1 day after neurotoxin administration, and this increase declined to basal levels by day 7. There was no significant increase found in the substantia nigra at any of the time points investigated. This same lesion paradigm produced dopamine depletions of 90-95% in the striatum and 63-80% in the substantia nigra by 14 to 28 days post 6-OHDA. Protein carbonyl and HNE levels were also measured in middle-aged and aged animals 1 day after striatal 6-OHDA. Both protein carbonyl and HNE levels were increased in the striatum of middle-aged and aged animals treated with 6-OHDA, but the increases were not as great as those observed in the young adult animals. Similar to the young animals, there were no increases in either marker in the substantia nigra of the middle-aged and aged animals. There was a trend for an age-dependent increase in basal amounts of oxidative stress markers when comparing the non-lesioned side of the brains of the three age groups. These results support that an early event in the course of dopamine depletion following intrastriatal 6-OHDA administration is the generation of oxidative stress. Keywordsreactive oxygen species; protein carbonyls; 4-hydroxynonenal; striatum; substantia nigra; aging; Fischer-344 rat Parkinson's disease (PD) stems from the loss of dopamine (DA) caused by the degeneration of the dopaminergic neurons of the substantia nigra. The nature of this degeneration remains unclear, although current theories suggest that reactive oxygen species (ROS) are involved in some capacity early in the disease process (Jenner, 2003). One of the earliest changes in patients with PD and incidental Lewy body disease is the loss of glutathione (Sian et al., 1994,Owen et al., 1996. Post mortem tissue from PD patients has been shown to contain elevated levels Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Yoritaka et al., 1996), protein carbonyls (Alam et...

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“…Hydrogen peroxide also results in neuronal injury through impaired mitochondrial function and increased levels of pro-apoptotic gene products, such as CD95/Fas [56,178,231]. Externalization of membrane PS residues also occurs in neurons during anoxia [38], NO exposure [44], or during the administration of agents that induce the production of ROS, such as 6-hydroxydopamine [194].…”

Section: Alzheimer's Disease In the Aging Populationmentioning

confidence: 99%

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

Chong

Maiese

2005

Brain Research Reviews

135

121

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More than a century has elapsed since the description of Alois Alzheimer's patient Auguste D. Yet, the well-documented generation of β-amyloid aggregates and neurofibrillary tangles that define Alzheimer's disease is believed to represent only a portion of the cellular processes that can determine the course of Alzheimer's disease. Understanding of the complex nature of this disorder has evolved with an increased appreciation for pathways that involve the generation of reactive oxygen species and oxidative stress, apoptotic injury that leads to nuclear degradation in both neuronal and vascular populations, and the early loss of cellular membrane asymmetry that mitigates inflammation and vascular occlusion. Recent work has identified novel pathways, such as the Wnt pathway and the serine-threonine kinase Akt, as central modulators that oversee cellular apoptosis and the formation of neurofibrillary tangles through their downstream substrates that include glycogen synthase kinase-3β, Bad, and Bcl-x L . Other closely integrated pathways control microglial activation, release of inflammatory cytokines, and caspase and calpain activation for the processing of amyloid precursor protein, tau protein cleavage, and presenilin disposal. New therapeutic avenues that are just open to exploration, such as with nicotinamide adenine dinucleotide modulation, cell cycle modulation, metabotropic glutamate system modulation, and erythropoietin targeted expression, may provide both attractive and viable alternatives to treat Alzheimer's disease.

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Nerve Growth Factor Protects against 6-Hydroxydopamine-induced Oxidative Stress by Increasing Expression of Heme Oxygenase-1 in a Phosphatidylinositol 3-Kinase-dependent Manner

Cited by 233 publications

References 50 publications

Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson’s disease

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

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