Sensory Neurons and Schwann Cells Respond to Oxidative Stress by Increasing Antioxidant Defense Mechanisms

Vincent, Andrea M.; Kato, Koichi; McLean, Lisa L.; Soules, Mary E.; Feldman, Eva L.

doi:10.1089/ars.2008.2235

Cited by 99 publications

(89 citation statements)

References 84 publications

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“…13) Nrf2 controls not only HO-1 gene but also the genes of other antioxidant proteins, including SOD, catalase, and ferritin. 8,14,15) EPS may be associated with the increase of antioxidant protein expression. In this study, we examined the effects of EPS on the expression of HO-1, SOD, and catalase in rat Schwann cells.…”

Section: )mentioning

confidence: 99%

“…14,15) We examined whether EPS could alter SOD and catalase levels. SOD1 and catalase protein levels in Schwann cells treated with EPS were estimated by fluorescence microscopy studies and Western blot analysis (Fig.…”

Section: Effect Of Eps On Sod and Catalase Levels In Schwannmentioning

confidence: 99%

“…14) Nrf2 is usually retained in the cytoplasm as an inactive complex with its cytosolic repressor, Kelch-like ECH associated protein 1 (Keap1). 8,23,24) When the Keap1-Nrf2 complex is dissociated by some form of cellular stimuli, Nrf2 is translocated into the nucleus where it binds to ARE.…”

Section: )mentioning

confidence: 99%

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Epalrestat Upregulates Heme Oxygenase-1, Superoxide Dismutase, and Catalase in Cells of the Nervous System

Yama

Sato

Murao

et al. 2016

Biological & Pharmaceutical Bulletin

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Heme oxygenase (HO)-1 has potent antioxidant and anti-inflammatory functions. Recent studies have shown that the upregulation of HO-1 is beneficial to counteract neuroinflammation, making HO-1 a new therapeutic target for neurological diseases. We have reported that epalrestat (EPS), which is currently used for the treatment of diabetic neuropathy, increases HO-1 levels through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in bovine aortic endothelial cells. In this study, we tested the hypothesis that EPS upregulates HO-1 via Nrf2 activation in the component cells of the nervous system, by using rat Schwann cells and human SH-SY5Y cells. Treatment of Schwann cells with EPS at near-plasma concentration led to a dramatic increase in HO-1 levels. Nrf2 knockdown by small interfering RNA (siRNA) suppressed the EPS-induced HO-1 expression. EPS did not promote the intracellular accumulation of free ferrous ion and reactive oxygen species, by increasing ferritin via Nrf2 during HO-1 induction. Moreover, EPS stimulated the expression of superoxide dismutase 1 and catalase, which also are Nrf2 target gene products. It also markedly increased HO-1 levels in SH-SY5Y cells through the activation of Nrf2. We demonstrated for the first time that EPS upregulates HO-1, superoxide dismutase, and catalase by activating Nrf2. We suggest that EPS has the potential to prevent several neurological diseases. Key words epalrestat; heme oxygenase (HO)-1; superoxide dismutase (SOD); catalaseHeme oxygenase (HO)-1 is a stress-responsive enzyme that has anti-inflammatory, antioxidant, and cytoprotective functions. Expectations are high that the regulation and amplification of HO-1 by pharmacological approaches would lead to the discovery of novel drugs for the treatment of a variety of diseases.1) HO-1 has emerged as an anti-inflammatory therapeutic target.2) In particular, targeting HO-1 in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, has been reported.3) As HO-1 expression is involved in neuropathological changes, its regulation is essential for the development of new therapeutic approaches.3) However, such metalloporphyrins as cobalt protoporphyrin IX, which are prototypical inducers of HO-1 and commonly used in experimental cell culture and animal models, are not applicable to clinical interventions because of their high toxicity.2) It is expected that the upregulation of HO-1 by currently available pharmacological agents, whose safety and pharmacokinetics have already been confirmed clinically, would be useful for the treatment of a variety of diseases.The biochemical activities of heme degradation products and their metabolic derivatives contribute to the cytoprotective function of HO-1. HO-1 catalyzes the degradation of heme to produce ferrous iron, carbon monoxide, and biliverdin, the latter of which is subsequently converted into bilirubin. Carbon monoxide is involved in inflammation regulation.4) Bilirubin and biliverdin, which can scavenge peroxyl radicals, are cytoprotec...

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Section: )mentioning

confidence: 99%

Section: Effect Of Eps On Sod and Catalase Levels In Schwannmentioning

confidence: 99%

See 1 more Smart Citation

Epalrestat Upregulates Heme Oxygenase-1, Superoxide Dismutase, and Catalase in Cells of the Nervous System

Yama

Sato

Murao

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Surviving astrocytes present vigorous reaction around the injury site with increased immunorreactivity to the specific cell marker, glial fibrillary acidic protein (GFAP), and reexpression of vimentin (VIM) (5). Hyperglycemia found in diabetes mellitus is known to cause well-characterized morphological and functional changes in peripheral neurons and Schwann cells (6). Much less is known about the effects of hyperglycemia on CNS cells, mainly on glia.…”

Section: Introductionmentioning

confidence: 99%

Decreased astrocytic GFAP expression in streptozotocin-induced diabetes after gliotoxic lesion in the rat brainstem

Bondan

Martins

Viani

2013

Arq Bras Endocrinol Metab

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Objective: The aim of this study was to evaluate the effect of diabetic hyperglycemia on astrocyte function, estimated by means of glial fibrillary acidic protein -GFAP -immunohistochemical expression. Materials and methods: Adult male rats received a single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10 days later to a single injection of 10 microlitres 0.1% EB solution or 0.9% saline solution into the cisterna pontis. Ten microliters of 0.1% EB or 0.9% saline solution were also injected in non-diabetic rats. Animals were anesthetized and perfused through the heart 15 and 31 days after EB or saline injection, and brainstem sections were collected for ultrastructural analysis and GFAP immunohistochemical staining. Results: The GFAP brown-stained areas were evaluated by colorimetry using a computerized image analysis system and the results have shown that diabetes hindered the increase of GFAP astrocyte expression in the EB-injected group compared to non-diabetic animals. However, diabetes did not affect GFAP response in the saline-injected group or in control animals. Conclusion: Streptozotocin-induced diabetic condition reduced astrocytic GFAP expression following gliotoxic injury. Arq Bras Endocrinol Metab. 2013;57(6):431-6 Keywords Astrocytes; GFAP; central nervous system; diabetes mellitus; ethidium bromide RESUMO Objetivo: O objetivo deste estudo foi avaliar o efeito da hiperglicemia na função astrocitária, estimada pela expressão imuno-histoquímica da proteína glial fibrilar ácida -GFAP. Materiais e métodos: Ratos machos adultos receberam uma injeção intravenosa única de estreptozotocina (50 mg/kg) e foram submetidos, 10 dias após, à injeção de 10 microlitros de solução de BE 0,1% ou de salina 0,9% na cisterna pontina. Dez microlitros de BE 0,1% ou salina 0,9% foram também injetados em ratos não diabéticos. Os animais foram anestesiados e perfundidos por via intracardíaca aos 15 e 31 dias pós-injeção de BE ou salina, e amostras de tronco encefálico foram coletadas para estudo ultraestrutural e análise imuno-histoquímica para a GFAP. Resultados: Utilizando um sistema computadorizado de análise de imagens, os resultados das áreas coradas em marrom pela GFAP, medidas por colorimetria, mostram que o diabetes reduziu o aumento de expressão dessa proteína no grupo injetado com BE em comparação aos animais não diabéticos, mas não alterou a resposta no grupo injetado com salina ou nos controles diabéticos. Conclusão: O estado diabético induzido pela estreptozotocina reduziu a expressão astrocitária de GFAP após dano gliotóxico. Arq Bras Endocrinol Metab. 2013;57(6):431-6 Descritores Astrócitos; GFAP; sistema nervoso central; diabetes melito; brometo de etídio

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“…Hyperglycemia found in diabetes mellitus is known to cause well described morphological and functional changes in peripheral neurons and Schwann cells (7). Much less is understood about the effects of hyperglycemia on CNS cells, mainly on glia.…”

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confidence: 99%

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats

Bondan

Martins

Bernardi

2015

Arch. Endocrinol. Metab.

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Objective: The diabetic state induced by streptozotocin injection is known to impair oligodendroglial remyelination in the rat brainstem following intracisternal injection with the gliotoxic agent ethidium bromide (EB). In such experimental model, propentofylline (PPF) recently showed to improve myelin repair, probably due to its neuroprotective, antiinflammatory and antioxidant effects. The aim of this study was to evaluate the effect of PPF administration in diabetic rats submitted to the EB-demyelinating model. Materials and methods: Adult male rats, diabetic or not, received a single injection of 10 microlitres of 0.1% EB solution into the cisterna pontis. For induction of diabetes mellitus the streptozotocin-diabetogenic model was used (50 mg/kg, intraperitoneal route -IP). Some diabetic rats were treated with PPF (12.5 mg/kg/day, IP route) during the experimental period. The animals were anesthetized and perfused from 7 to 31 days after EB injection and brainstem sections were collected for analysis of the lesions by light and transmission electron microscopy. Results: Diabetic rats injected with EB showed larger amounts of myelin-derived membranes in the central areas of the lesions and considerable delay in the remyelinating process played by surviving oligodendrocytes and invading Schwann cells after the 15 th day. On the other hand, diabetic rats that received PPF presented lesions similar to those of non-diabetic animals, with rapid remyelination at the edges of the lesion site and fast clearance of myelin debris from the central area. Conclusion: The administration of PPF apparently reversed the impairment in remyelination induced by the diabetic state. Arch Endocrinol Metab. 2015;59(1):47-53

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Sensory Neurons and Schwann Cells Respond to Oxidative Stress by Increasing Antioxidant Defense Mechanisms

Cited by 99 publications

References 84 publications

Epalrestat Upregulates Heme Oxygenase-1, Superoxide Dismutase, and Catalase in Cells of the Nervous System

Epalrestat Upregulates Heme Oxygenase-1, Superoxide Dismutase, and Catalase in Cells of the Nervous System

Decreased astrocytic GFAP expression in streptozotocin-induced diabetes after gliotoxic lesion in the rat brainstem

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats

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