Involvement of the Nrf2/HO-1 signaling pathway in sulfuretin-induced protection against amyloid beta25–35 neurotoxicity

Kwon, Seung-Hwan; Ma, Shi-Xun; Hwang, Ji-Young; Lee, S.-Y.; Jang, Choon‐Gon

doi:10.1016/j.neuroscience.2015.07.030

Cited by 71 publications

(41 citation statements)

References 35 publications

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“…In this study, we observed that otopathogenic P. aeruginosa induces death of human MDMs and mouse BMMϕ as determined by LDH release in the cell culture supernatants and ethidium homodimer-I staining. LDH is the most acceptable and reliable marker for determining host cell death (Kwon et al, 2015; Park et al, 2015; Lv et al, 2016) . Ethidium homodimer-I is a fluorescent nuclear stain that penetrates dead cells due to disrupted plasma membrane and increases intensity after binding to DNA (Eidet et al, 2015; McCanna et al, 2015; Yoeruek et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

et al. 2016

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Otitis media (OM) is a broad term describing a group of infectious and inflammatory disorders of the middle ear. Despite antibiotic therapy, acute OM can progress to chronic suppurative otitis media (CSOM) characterized by ear drum perforation and purulent discharge. Pseudomonas aeruginosa is the most common pathogen associated with CSOM. Although, macrophages play an important role in innate immune responses but their role in the pathogenesis of P. aeruginosa-induced CSOM is not known. The objective of this study is to examine the interaction of P. aeruginosa with primary macrophages. We observed that P. aeruginosa enters and multiplies inside human and mouse primary macrophages. This bacterial entry in macrophages requires both microtubule and actin dependent processes. Transmission electron microscopy demonstrated that P. aeruginosa was present in membrane bound vesicles inside macrophages. Interestingly, deletion of oprF expression in P. aeruginosa abrogates its ability to survive inside macrophages. Our results suggest that otopathogenic P. aeruginosa entry and survival inside macrophages is OprF-dependent. The survival of bacteria inside macrophages will lead to evasion of killing and this lack of pathogen clearance by phagocytes contributes to the persistence of infection in CSOM. Understanding host–pathogen interaction will provide novel avenues to design effective treatment modalities against OM.

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Section: Discussionmentioning

confidence: 99%

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

et al. 2016

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“…Sulfuretin (Fig. ), a flavonoid glycoside, significantly attenuated the decrease in cell viability and accumulation of ROS associated with Aβ25‐35‐induced neurotoxicity in neuronal cells . Sulfuretin stimulated the activation of Nrf2, resulting in increased expression of the antioxidant Nrf2‐target gene heme oxygenase‐1 (HO‐1).…”

Section: Oxidative Stress In Neurodegenerative Disease and The Countementioning

confidence: 99%

The role of Nrf2 signaling in counteracting neurodegenerative diseases

2018

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The transcription factor Nrf2 (nuclear factor‐erythroid 2 p45‐related factor 2) functions at the interface of cellular redox and intermediary metabolism. Nrf2 target genes encode antioxidant enzymes, and proteins involved in xenobiotic detoxification, repair and removal of damaged proteins and organelles, inflammation, and mitochondrial bioenergetics. The function of Nrf2 is altered in many neurodegenerative disorders, such as Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Friedreich's ataxia. Nrf2 activation mitigates multiple pathogenic processes involved in these neurodegenerative disorders through upregulation of antioxidant defenses, inhibition of inflammation, improvement of mitochondrial function, and maintenance of protein homeostasis. Small molecule pharmacological activators of Nrf2 have shown protective effects in numerous animal models of neurodegenerative diseases, and in cultures of human cells expressing mutant proteins. Targeting Nrf2 signaling may provide a therapeutic option to delay onset, slow progression, and ameliorate symptoms of neurodegenerative disorders.

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“…A very recent study using SH-SY5Y cells has revealed that sulfuretin, one of the major flavonoid glycosides, induces Nrf2-dependent HO-1 expression and has preventive and/or therapeutic potential for the management of Alzheimer's disease. 47) In addition, berberine, a well-known alkaloid, protects SH-SY5Y cells from cell death induced by Parkinson's disease related neurotoxin 6-hydroxydopamine through the induction of HO-1. 48) From the findings of the present study, we expect that the pharmacological actions of EPS would lead to breakthroughs in drug discovery and development.…”

Section: )mentioning

confidence: 99%

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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Involvement of the Nrf2/HO-1 signaling pathway in sulfuretin-induced protection against amyloid beta25–35 neurotoxicity

Cited by 71 publications

References 35 publications

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

The role of Nrf2 signaling in counteracting neurodegenerative diseases

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

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