Sulforaphane Induces Thioredoxin through the Antioxidant-Responsive Element and Attenuates Retinal Light Damage in Mice

Tanito, Masaki; Masutani, Hiroshi; Kim, Yong-Chul; Nishikawa, Mai; Ohira, Akihiro; Yodoi, Junji

doi:10.1167/iovs.04-1120

Cited by 179 publications

(135 citation statements)

References 43 publications

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“…SF protects immature hippocampal neurons against death caused by exposure to hemin or to oxygen and glucose-deprivation (25). SF induces thioredoxin expression and attenuates retinal light damage in mice (26). It also has been reported that SF protects against 6-OHDA-induced cytotoxicity.…”

Section: Discussionmentioning

confidence: 96%

Sulforaphane protects against 6-hydroxydopamine-induced cytotoxicity by increasing expression of heme oxygenase-1 in a PI3K/Akt-dependent manner

Jin¹

2011

Mol Med Report

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Abstract. Parkinson's disease (PD) is a progressive neurodegenerative disorder with selective loss of dopaminergic neurons in the substantia nigra. Evidence suggests that oxidative stress is involved in the pathogenesis of PD. Sulforaphane (SF), a naturally occurring isothiocyanate, has been shown to protect against oxidative stress by inducing the expression of various NF-E2-related factor-2 (Nrf2) responsive genes. Previous studies have shown that SF protects dopaminergic neurons against PD-related neurotoxin 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. However, the molecular mechanisms by which SF protects against 6-OHDA-induced cytotoxicity are poorly elucidated. In this study, we found that pretreatment with SF significantly reduced 6-OHDAinduced caspase-3 activation and subsequent cell death. SF also increased heme oxygenase-1 (HO-1) expression, which conferred protection against 6-OHDA-induced cytotoxicity. Furthermore, SF induced the translocation of Nrf2 into the nucleus and activated PI3K/Akt, a pathway that is involved in SF-induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. These results suggest that SF inhibits 6-OHDA-induced cytotoxicity through increasing HO-1 expression in a PI3K/Akt-dependent manner.

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Section: Discussionmentioning

confidence: 96%

Sulforaphane protects against 6-hydroxydopamine-induced cytotoxicity by increasing expression of heme oxygenase-1 in a PI3K/Akt-dependent manner

Jin¹

2011

Mol Med Report

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“…SF protects immature hippocampal neurons against death caused by exposure to hemin or to oxygen and glucosedeprivation (24). SF has been shown to induce thioredoxin expression and attenuates retinal light damage in mice (25). It has also been reported that SF may serve as a potential candidate for the treatment and/or prevention of PD.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by sulforaphane through the activation of Nrf2 nuclear translocation

Jin¹

2012

Mol Med Report

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Abstract. Endoplasmic reticulum (ER) stress plays a key role in the development of neurodegenerative diseases, including Parkinson's disease (PD). Sulforaphane (SF) is a natural drug derived from isothiocyanate found in cruciferous vegetables. Although there are reports indicating that SF is a potential candidate for PD treatment, there have been no reports on the effects of SF on ER stress in PD. In this study, we investigated the cytoprotective effects of SF on 6-hydroxydopamine (6-OHDA)-induced ER stress in rat PC12 cells. Pre-treatment with SF elicited cytoprotection against 6-OHDA-induced cytotoxicity. Consistent with its cytoprotective action, SF significantly inhibited subsequent ER stress, including the expression of Bip and the C/EBP homologous protein. We also found that transfection with NF-E2-related factor-2 (Nrf2) siRNA reversed the inhibitory effects of SF on 6-OHDA-induced ER stress responses.In conclusion, our results show that SF can prevent ER stress response induced by 6-OHDA through the activation of Nrf2. SF may be a therapeutic candidate for the treatment of ER stress-associated neural diseases, including PD.

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“…RPE cell death plays a major role in the pathogenesis of age-related macular degeneration, the leading cause of blindness in the population Ͼ60 years of age in the developed world (2). Possible reasons given for the degeneration of RPE cells are their exposure to high oxidative stress and damaging irradiation (2)(3)(4)(5)(6).…”

mentioning

confidence: 99%

Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

Seagle

Rezai

Kobori

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

104

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Time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to study melanin free radicals in human retinal pigment epithelium (RPE) cells and tyrosine-derived synthetic melanin. TREPR signal traces from RPE cells reveal in vivo light-induced melanin free radical photochemistry in more detail than previously known. Electron spin polarization reflecting a non-Boltzmann population within the energy levels of the spin system is observed in RPE cells as the result of the triplet state photoproduction and subsequent disappearance of free radicals in the melanin polymer. In a set of RPE cells cultured from individual sources, differences in optical absorption, continuous wave EPR spectra, and TREPR signals were correlated with apoptosis assays performed by flow cytometry. Continuous wave EPR spectra of RPE cells and TREPR of acidified synthetic melanin suggest that increased melanin aggregation provides an increase in photoprotection in the RPE cells that are relatively less susceptible to blue light-induced apoptosis.continuous wave EPR ͉ electron spin polarization ͉ time-resolved EPR I n the eye, retinal pigment epithelium (RPE) is a monolayer of cuboidal cells between the photoreceptors and choriocapillaris of the eye and is specialized to uptake, phagocytize, and recycle the outer segment of photoreceptors and retinaldehyde, the chromophore of rhodopsin (1). RPE cell death plays a major role in the pathogenesis of age-related macular degeneration, the leading cause of blindness in the population Ͼ60 years of age in the developed world (2). Possible reasons given for the degeneration of RPE cells are their exposure to high oxidative stress and damaging irradiation (2-6).The pigment melanin, found in RPE cells, is a heterogeneous polymer consisting of various monomers believed to be oxidation products of dopa (dihydroxyphenylalinine) derived from tyrosine (7). Melanin contains intrinsic, indolesemiquinone-like doublet-state radicals (8, 9). Extrinsic indolesemiquinone-like radicals are reversibly photogenerated under visible or UV irradiation (9). RPE melanin serves a photoprotective role by absorbing radiation and scavenging free radicals and reactive oxygen species (ROS) (8-11). Evidence also exists for a phototoxic role for melanin in RPE cells, especially in aged cells, including measurable ROS photoproduction (8,(12)(13)(14)(15)(16)(17)(18). Electron paramagnetic resonance (EPR) spectroscopy enables a sensitive and nondestructive analysis and differentiation of natural melanin (9,19,20). The photophysical, redox, and aggregation properties of melanin as well as its ability to bind metals, proteins, and drugs have stimulated numerous studies in chemical, physical, and medical research (8, 9). The diversity and interrelations of its properties and the lack of chemical structures have hampered a clear understanding of the roles of melanin in RPE cells (8,9). Nanosecond time-resolved (TR) EPR studies have not been reported despite the relevance of TREPR to the study of melanin photochemistry (9). El...

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Sulforaphane Induces Thioredoxin through the Antioxidant-Responsive Element and Attenuates Retinal Light Damage in Mice

Abstract: SF induced Trx in murine retina and effectively reduced retinal light damage. Evidence suggests that the ARE is involved in the mechanism of Trx induction by SF in RPE cells.

Cited by 179 publications

References 43 publications

Sulforaphane protects against 6-hydroxydopamine-induced cytotoxicity by increasing expression of heme oxygenase-1 in a PI3K/Akt-dependent manner

Sulforaphane protects against 6-hydroxydopamine-induced cytotoxicity by increasing expression of heme oxygenase-1 in a PI3K/Akt-dependent manner

Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by sulforaphane through the activation of Nrf2 nuclear translocation

Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

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