Sulforaphane Can Protect Lens Cells Against Oxidative Stress: Implications for Cataract Prevention

Liu, Hanruo; Smith, Alan; Lott, Martin; Bao, Yongping; Bowater, Richard P.; Reddan, John R.; Wormstone, I. Michael

doi:10.1167/iovs.13-11664

Cited by 46 publications

(55 citation statements)

References 48 publications

(59 reference statements)

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“…Under terminal UPR, the level of Nrf2 decreases due to proteasomal degradation and proteolysis by m-calpain and caspase-3 and caspase-1 [37, 38]. Recently, Liu and his colleagues demonstrated Nrf2 translocation into the nucleus in response to sulforaphane in HLECs, which coincides with lenticular protection against oxidative stress [39]. …”

Section: Introductionmentioning

confidence: 99%

Selenite cataracts: Activation of endoplasmic reticulum stress and loss of Nrf2/Keap1-dependent stress protection

Periyasamy

Bidasee

Shinohara

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Cataract-induced by sodium selenite in suckling rats is one of the suitable animal models to study the basic mechanism of human cataracts formation. The aim of this present investigation is to study the endoplasmic reticulum (ER) stress-mediated activation of unfolded protein response (UPR), overproduction of reactive oxygen species (ROS), and suppression of Nrf2/Keap1-dependent antioxidant protection through endoplasmic reticulum-associated degradation (ERAD) pathway and Keap1 promoter DNA demethylation in human lens epithelial cells (HLECs) treated with sodium selenite. Lenses enucleated from sodium selenite injected rats generated overproduction of ROS in lens epithelial cells and newly formed lens fiber cells resulting in massive lens epithelial cells death after 1–5 days. All these lenses developed nuclear cataracts after 4–5 days. Sodium selenite treated HLECs induced ER stress and activated the UPR leading to release of Ca2+ from ER, ROS overproduction and finally HLECs death. Sodium selenite also activated the mRNA expressions of passive DNA demethylation pathway enzymes such as Dnmt1, Dnmt3a, and Dnmt3b, and active DNA demethylation pathway enzyme, Tet1 leading to DNA demethylation in the Keap1 promoter of HLECs. This demethylated Keap1 promoter results in overexpression of Keap1 mRNA and protein. Overexpression Keap1 protein suppresses the Nrf2 protein through ERAD leading to suppression of Nrf2/Keap1 dependent antioxidant protection in the HLECs treated with sodium selenite. As an outcome, the cellular redox status is altered towards lens oxidation and results in cataract formation.

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Section: Introductionmentioning

confidence: 99%

Selenite cataracts: Activation of endoplasmic reticulum stress and loss of Nrf2/Keap1-dependent stress protection

Periyasamy

Bidasee

Shinohara

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Nrf2 activation and the indirect antioxidant effects of sulforaphane appear to be ubiquitous; they have been observed in the liver [30][31][32]41,59,60], kidney [60], lungs [60][61][62][63], lens [58], central nervous system [49,60], immune system [50], choroid plexus [51], small intestine [9], large intestine [60], prostate [60], retinal pigment epithelial cells [34,39,64], corneal epithelial cells [55], astroglial cells [54], fetal neural crest cells [52], neuroblastoma cells [36], insulin-secreting pancreatic cells [65], differentiated peripheral blood neutrophils [53], endothelial cells [40], osteoblasts [37], and keratinocytes [33][34][35].…”

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confidence: 99%

A Glance at… Broccoli, glucoraphanin, and sulforaphane

Glade

Meguid²

2015

Nutrition

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“…However, whether this compound could be useful in cataract prevention remains to be determined. The beneficial effect of sulforaphane in protecting the lens against cataract formation is also predictable from its preventive effect against lens opacification induced by hydrogen peroxide in vitro 60. It has also been reported to protect against light-induced damage to retinal pigment epithelium in isolated mouse eye cup preparations 61…”

Section: Resultsmentioning

confidence: 98%

Sulforaphane-induced transcription of thioredoxin reductase in lens: possible significance against cataract formation

Varma¹,

Chandrasekaran²,

Ковтун³

2013

OPTH

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PurposeSulforaphane is a phytochemically derived organic isothiocyanate 1-isothiocyanato-4-methylsulfinyl-butane present naturally in crucifers, including broccoli and cauliflower. Biochemically, it has been reported to induce the transcription of several antioxidant enzymes. Since such enzymes have been implicated in preventing cataract formation triggered by the intraocular generation of oxy-radical species, the purpose of this investigation was to examine whether it could induce the formation of antioxidant enzymes in the eye lens. Thioredoxin reductase (TrxR) was used as the target of such induction.MethodsMice lenses were cultured for an overnight period of 17 hours in medium 199 fortified with 10% fetal calf serum. Incubation was conducted in the absence and presence of sulforaphane (5 μM). Subsequently, the lenses were homogenized in phosphate-buffered saline (PBS), followed by centrifugation. TrxR activity was determined in the supernatant by measuring the nicotinamide adenine dinucleotide phosphate (reduced) (NADPH)-dependent reduction of 5,5′-dithiobis-2-nitrobenzoic acid (DTNB). Non-specific reduction of DTNB was corrected for by conducting parallel determinations in the presence of aurothiomalate. The reduction of DTNB was followed spectrophotometrically at 410 nm.ResultsThe activity of TrxR in the lenses incubated with sulforaphane was found to be elevated to 18 times of that observed in lenses incubated without sulforaphane. It was also noticeably higher in the lenses incubated without sulforaphane than in the un-incubated fresh lenses. However, this increase was much lower than that observed for lenses incubated with sulforaphane.ConclusionSulforaphane has been found to enhance TrxR activity in the mouse lens in culture. In view of the protective effect of the antioxidant enzymes and certain nutrients against cataract formation, the findings suggest that it would, by virtue of its ability to enhance the activity of such enzymes, prevent the tissue against oxidative stress that leads to cataract formation. Additional studies with the activities of other antioxidant enzymes such as quinone oxidoreductase and the levels of Nrf2 are in progress.

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Sulforaphane Can Protect Lens Cells Against Oxidative Stress: Implications for Cataract Prevention

Abstract: The dietary component SFN demonstrates an ability to protect human lens cells against oxidative stress and thus could potentially delay the onset of cataract.

Cited by 46 publications

References 48 publications

Selenite cataracts: Activation of endoplasmic reticulum stress and loss of Nrf2/Keap1-dependent stress protection

Selenite cataracts: Activation of endoplasmic reticulum stress and loss of Nrf2/Keap1-dependent stress protection

A Glance at… Broccoli, glucoraphanin, and sulforaphane

Sulforaphane-induced transcription of thioredoxin reductase in lens: possible significance against cataract formation

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