Lutein, a Nonprovitamin A, Activates the Retinoic Acid Receptor to Induce HAS3-Dependent Hyaluronan Synthesis in Keratinocytes

Abstract

Carotenoids have been reported to have potent antioxidant activities and to protect tissues and cells from certain diseases and environmental insults. The molecular mechanism of the action of provitamin A carotenoids such as β-carotene and β-cryptoxanthin is mediated in part by retinoic acid, an active form of provitamin A, but the molecular basis of the biological activities of non-provitamin A carotenoids such as lutein, zeaxanthin, and astaxanthin is not fully understood. In this study, we investigated to determine whether the actions of non-provitamin A carotenoids are mediated via retinoid signaling by monitoring retinoic acid receptor (RAR)-dependent hyaluronan production in cultured human keratinocytes. Not only β-carotene and β-cryptoxanthin, but also lutein, zeaxanthin, and astaxanthin, upregulated HAS3 gene expression and were followed by hyaluronan synthesis. We found that LE540, an antagonist of retinoic acid receptors, abolished lutein dependent hyaluronan synthesis and that lutein significantly increased retinoic acid responsive element (RARE)-driven transcript acitivity. In addition, we found that citral, an inhibitor of retinal dehydrogenases, decreased lutein-stimulated hyaluronan synthesis, indicating that lutein metabolites rather than lutein itself act as an RAR ligand in RAR-mediated transcription activity in keratinocytes. A series of non-provitamin A can be substituted for retinoids and should be considered as a potential means of improving skin health.

Silk fibroin film from golden‐yellow Bombyx mori is a biocomposite that contains lutein and promotes axonal growth of primary neurons

“…In this context it has to be pointed out that lutein, known as non‐provitamin A, is not catabolized to retinoic acid. However, recent evidence demonstrated that lutein is capable to activate signaling cascades of retinoic acid receptors in keratinocytes and macrophages in vitro . Thus, it is plausible to suppose that a direct effect of lutein, rather than an indirect effect of its catabolites, is responsible for the molecular mechanism underpinning the observed increased neurite outgrowth.…”

“…These studies set the scene for the use of SF in neuroregenerative medicine. In this context, delivery of carotenoids derivatives has been proposed as an alternative therapeutic strategy to nerve growth factors in neuroregenerative medicine to overcome major problems such as high degradation rate and low bio‐availability of growth factors at sites of injury . Moreover, neuroprotective effects of carotenoids related to their antioxidant properties, have been demonstrated in acute and chronic pathophysiologies that involve excessive oxidative stress such as Ischemia and Alzheimer's disease .…”

The Potential Use of Marine Microalgae and Cyanobacteria in Cosmetics and Thalassotherapy

“…It has been observed that ß-cryptoxanthin (a carotene found in Dunaliella salina, among other microalgae) [35], as well as being an anti-inflammatory, is also able to induce the synthesis of hyaluronic acid [36], a glycosaminoglycan involved in skin hydration.…”

Plastids of Marine Phytoplankton Produce Bioactive Pigments and Lipids

“…Despite of these studies the molecular mechanism related to the biological activities of Asta is not yet fully understood. In a recent study, Sayo et al [114] investigated whether the actions of nonprovitamin A carotenoids including Asta are mediated via retinoid signaling in cultured human keratinocytes. They found that β-carotene, β-cryptoxanthin, lutein, zeaxanthin, and Asta, upregulated HAS3 gene expression and stimulated hyaluronan synthesis.…”