ABSTRACT
Carotenoids, in particular astaxanthin, possess potent antioxidant capabilities. Astaxanthin also induces NF-E2-related factor 2 (Nrf2), which plays a major regulatory role in the antioxidative response. However, little is known whether the carotenoid, by-products of astaxanthin, activate Nrf2. Toward this end, we screened eight astaxanthin analogs for Nrf2 activation in murine photoreceptor cell line, 661 W, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In addition, we monitored cell death in 661 W cells pretreated with astaxanthin analogs or only pretreated for 6 h with astaxanthin analogs and then exposed to light. Furthermore, we quantified the reactive oxygen species (ROS) production. Cell death was quantified after light exposure by nuclear staining. Nrf2-controlled genes Ho-1, Nqo-1, and Gclm by qRT-PCR and Nrf2 in the nucleus were upregulated in 661 W cells exposed astaxanthin, adonixanthin, echinenone, and lycopene. Moreover, astaxanthin, adonixanthin, echinenone, ß-carotene, adonirubin, and lycopene, but not canthaxanthin, suppressed ROS production and protected cells against light-induced damage. Moreover, pretreatment with adonixanthin or lycopene only before light exposure protected against light-induced cell damage and Nrf2 silencing canceled these effects. These findings indicate that the more potent astaxanthin analogs, adonixanthin and lycopene, protect against light-induced cell damage through not only an anti-oxidative response but also through Nrf2 activation.
Subject(s)
Carotenoids/pharmacology , Cell Death/drug effects , Light/adverse effects , NF-E2-Related Factor 2/metabolism , Photoreceptor Cells/drug effects , Photoreceptor Cells/pathology , Animals , Antioxidants/pharmacology , Cell Line , Gene Silencing , Lycopene , Mice , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/physiology , Photoreceptor Cells/metabolism , Reactive Oxygen Species/metabolismABSTRACT
The retina is highly sensitive to oxidative stress because of its high consumption of oxygen associated with the phototransductional processes. Recent findings have suggested that oxidative stress is involved in the pathology of age-related macular degeneration, a progressive degeneration of the central retina. A well-known environmental risk factor is light exposure, as excessive and continuous light exposure can damage photoreceptors. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that controls antioxidative responses and phase 2 enzymes. Thus, we hypothesized that RS9, a specific activator of Nrf2, decreases light-induced retinal cell death in vivo and in vitro. Nrf2 was detected in the nucleus of the 661W cells exposed to RS9 and also after light exposure, and the Nrf2-antioxidant response element binding was increased in 661W cells after exposure to RS9. Consequentially, the expression of the phase 2 enzyme's mRNAs of Ho-1, Nqo-1, and Gclm genes was increased in 661W cells after exposure to RS9. Furthermore, RS9 decreased the light-induced death of 661W cells (2500 lux, 24 h), and also reduced the functional damages and the histological degeneration of the nuclei in the outer nuclear layer or the retina in the in vivo studies (8000 lux, 3 h). Heme oxygenase-1 was increased after light exposure, and Nrf2 was translocated into the nucleus after light exposure in vivo. Silencing of Ho-1 reduced the protective effects of RS9 against light-induced death of 661W cells. These findings indicate that RS9 has therapeutic potential for retinal diseases that are aggravated by light exposure.
Subject(s)
Cell Death/drug effects , Ependymoglial Cells/drug effects , Light/adverse effects , Photoreceptor Cells/drug effects , Triterpenes/pharmacology , Animals , Cell Death/radiation effects , Cell Line, Transformed , Cell Nucleolus/drug effects , Cell Nucleolus/radiation effects , Cytosol/drug effects , Cytosol/radiation effects , Ependymoglial Cells/cytology , Ependymoglial Cells/radiation effects , Gene Expression Regulation/drug effects , Gene Expression Regulation/radiation effects , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , In Vitro Techniques , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , NF-E2 Transcription Factor/genetics , NF-E2 Transcription Factor/metabolism , Photoreceptor Cells/radiation effects , Protein Biosynthesis/drug effects , Protein Biosynthesis/radiation effects , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Retina/cytology , Retinal Degeneration/etiology , Retinal Degeneration/prevention & control , Time Factors , Triterpenes/chemistryABSTRACT
We report that charged colloids exhibit thermoreversible crystallization via the adsorption of ionic surfactants onto particle surfaces. Due to the temperature dependence of the adsorption quantity, the colloids crystallized upon cooling and melted upon heating. To clarify the influences of surfactant adsorption on the crystallization, polystyrene (PS) particles dispersed in ethylene glycol (EG)/water mixtures were employed, enabling continuous tuning of the adsorption quantity by changing the EG concentration. The thermoreversible crystallization/melting behavior was found to be mainly attributable to changes in the ionic strength of the medium resulting from variation in the concentration of the non-adsorbed ionic surfactant molecules with temperature. We expect that the present findings will be useful for fine control of colloidal crystallization and the further study of colloidal crystallization in low permittivity media.
