Nitric Oxide and Cellular Stress Response in Brain Aging and Neurodegenerative Disorders

Calabrese, Vittorio; Mancuso, Cesare; Marco, C. De; Stella, A. M. Giuffrida; Butterfield, D. Allan

doi:10.1016/b978-044452809-4/50145-9

Cited by 74 publications

(134 citation statements)

References 123 publications

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“…The vitagene family is composed of the heat shock proteins HO-1 (also called Hsp32), Hsp70, by the thioredoxin system and by sirtuin proteins [22][23][24]. We therefore evaluated the expression levels of cellular stress response proteins in the CSF, plasma and lymphocytes in control and in MS patients.…”

Section: Resultsmentioning

confidence: 99%

Redox regulation of cellular stress response in multiple sclerosis

Pennisi

Cornelius

Cavallaro

et al. 2011

Biochemical Pharmacology

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Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease with characteristic foci of inflammatory demyelination in the brain, spinal cord, and optic nerves. Recent studies have demonstrated not only that axonal damage and neuronal loss are significant pathologic components of MS, but that this neuronal damage is thought to cause the permanent neurologic disability often seen in MS patients. Emerging finding suggests that altered redox homeostasis and increased oxidative stress, primarily implicated in the pathogenesis of MS, are a trigger for activation of a brain stress response. Relevant to maintenance of redox homeostasis, integrated mechanisms controlled by vitagenes operate in brain in preserving neuronal survival during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. In the present study we assess stress response mechanisms in the CSF, plasma and lymphocytes of control patients compared to MS patients. We found that the levels of vitagenes Hsp72, Hsc70, HO-1, as well as oxidative stress markers carbonyls and hydroxynonenals were significantly higher in the blood and CSF of MS patients than in control patients. In addition, an increased expression of Trx and sirtuin 1, together with a decrease in the expression of TrxR were observed. Our data strongly support a pivotal role for redox homeostasis disruption in the pathogenesis of MS and, consistently with the notion that new therapies that prevent neurodegeneration through nonimmunomodulatory mechanisms can have a tremendous potential to work synergistically with current MS therapies, unravel important targets for new cytoprotective strategies

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Section: Resultsmentioning

confidence: 99%

Redox regulation of cellular stress response in multiple sclerosis

Pennisi

Cornelius

Cavallaro

et al. 2011

Biochemical Pharmacology

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“…Kumar et al have shown that antioxidative treatments restore behavioral disorders and antioxidative defense mechanisms in 3-NP treated animals [10,11,31] . In the CNS, cells are able to defend against oxidative stress using several resources, including vitamins, bioactive molecules, lipoic acid, enzymes (such as SOD, GSH, GPx, HO-1, and NQO1), and redox sensitive protein transcription factors (such as AP-1, Nrf2, and HSF) [32,33] . Hsp70, also referred to as Hsp72, which has a cytoprotective function, is induced in many neurodegenerative disorders [26] .…”

Section: Wwwchinapharcom Gao Y Et Almentioning

confidence: 99%

“…A large number of reports have demonstrated that panax ginseng possesses a number of beneficial effects in the CNS [1,[27][28][29][30][31][32][33][34][35][36] . Protopanaxtriol (Ppt) is a neuroprotective ginseng extract.…”

Section: Introductionmentioning

confidence: 99%

Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington's disease

Gao

Chu

et al. 2015

Acta Pharmacol Sin

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Aim: Protopanaxtriol (Ppt) is extracted from Panax ginseng Mayer. In the present study, we investigated whether Ppt could protect against 3-nitropropionic acid (3-NP)-induced oxidative stress in a rat model of Huntington's disease (HD) and explored the mechanisms of action. Methods: Male SD rats were treated with 3-NP (20 mg/kg on d 1, and 15 mg/kg on d 2-5, ip). The rats received Ppt (5, 10, and 20 mg/kg, po) daily prior to 3-NP administration. Nimodipine (12 mg/kg, po) or N-acetyl cysteine (NAC, 100 mg/kg, po) was used as positive control drugs. The body weight and behavior were monitored within 5 d. Then the animals were sacrificed, neuronal damage in striatum was estimated using Nissl staining. Hsp70 expression was detected with immunohistochemistry. Reactive oxygen species (ROS) generation was measured using dihydroethidium (DHE) staining. The levels of components in the Nrf2 pathway were measured with immunohistochemistry and Western blotting. Results: 3-NP resulted in a marked reduction in the body weight and locomotion activity accompanied by progressive striatal dysfunction. In striatum, 3-NP caused ROS generation mainly in neurons rather than in astrocytes and induced Hsp70 expression. Administration of Ppt significantly alleviated 3-NP-induced changes of body weight and behavior, decreased ROS production and restored antioxidant enzymes activities in striatum. Moreover, Ppt directly scavenged free radicals, increased Nrf2 entering nucleus, and the expression of its downstream products heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidase 1 (NQO1) in striatum. Similar effects were obtained with the positive control drugs nimodipine or NAC. Conclusion: Ppt exerts a protective action against 3-NP-induced oxidative stress in the rat model of HD, which is associated with its anti-oxidant activity.

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“…NO and other ROS and RNS exert important roles in the brain, such as neuromodulation, neurotransmission, and synaptic plasticity, but are also involved in pathologic processes such as neurodegeneration and neuroinflammation [14]. Acute and chronic inflammation induces an increased nitrogen monoxide formation and nitrosative stress.…”

Section: Role Of No and Cellular Stress Response In Brain Aging And Nmentioning

confidence: 99%

“…To endure different types of injuries, brain cells have developed integrated adaptive responses, termed longevity assurance processes, encompassing a number of genes dubbed vitagenes and components of the heat shock protein (HSP) system, including HSP70 and HSP32, to identify and control assorted forms of stress. Calabrese and colleagues [14] suggest that maintenance or recovery of the activity of vitagenes may delay the aging process and lower the occurrence of age-related diseases thereby providing prolongation of a healthy life span.…”

Section: Role Of No and Cellular Stress Response In Brain Aging And Nmentioning

confidence: 99%

Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species

Lahiri

Ghosh

Rogers

et al. 2010

Aging and Age-Related Disorders

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Role of nitric oxide in neurodegeneration and vulnerability of neuronal cells to nitric oxide metabolites and reactive oxygen species NO can also be released chemically from a group of compounds called NO donors, such as sodium nitroprusside (SNP). NO directly or through its metabolites is believed to be involved in several disorders, including Alzheimer's disease (AD). This chapter summarizes the role of NO and oxidative stress in neurodegeneration and describes the experimental evidence of increased vulnerability of neuronal cells to NO metabolites and other reactive oxygen species (ROS). As NO is a highly labile, unstable free gas, levels of the stable end products, such as nitrite and nitrate (NOx), were measured. When different cell types were treated with SNP, a significant level of NOx was detected in a time-and dose-dependent manner, which was more than the spontaneous release by SNP. Astrocytic, glial, and epithelial cell lines released significantly higher levels of NOx compared with neuronal cell lines after SNP treatment. Neuronal cells were more sensitive to SNP-induced cytotoxicity, as determined by lactate dehydrogenase assay. SNP-mediated toxicity is known to be due, in large part, to the accumulation of cyanide ions, and the ability of cells to protect themselves against this toxicity depends upon their levels of NO metabolites. Cell lines that generate more NOx, such as astrocytic and epithelial, are better protected against the SNP-induced toxicity than are less NOx-protecting neuronal cell lines. Our results suggest that various cell types metabolize SNP differently and that neuronal cell lines are more vulnerable than other cell types to SNP treatment. As neuronal cell lines lack an NO-generated protective mechanism, these cells are potentially primary targets for neurodegeneration by toxic agents including the free radicals and peroxynitrites.

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Nitric Oxide and Cellular Stress Response in Brain Aging and Neurodegenerative Disorders

Cited by 74 publications

References 123 publications

Redox regulation of cellular stress response in multiple sclerosis

Redox regulation of cellular stress response in multiple sclerosis

Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington's disease

Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species

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