Abstract
Astaxanthin, an antioxidant agent, can protect pancreatic β-cells of db/db mice from glucotoxicity and resolve chronic inflammation in adipose tissue. Nonetheless, the effects of astaxanthin on free-fatty-acid-induced inflammation and cellular stress in β-cells remain to be demonstrated. Meanwhile, palmitate enhances the secretion of pro-inflammatory adipokines monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF120). We therefore investigated the influence of astaxanthin on palmitate-stimulated MCP-1 and VEGF120 secretion in mouse insulinoma (MIN6) pancreatic β-cells. Furthermore, whether astaxanthin prevents cellular stress in MIN6 cells was also assessed. Pre-treatment with astaxanthin or with N-acetyl-cysteine (NAC) which is an antioxidant drug, significantly attenuated the palmitate-induced MCP-1 release through downregulation of phosphorylated c-Jun NH2-terminal protein kinase (JNK) pathways, and suppressed VEGF120 through the PI3K/Akt pathways relative to the cells stimulated with palmitate alone. In addition, palmitate significantly upregulated homologous protein (CHOP) and anti-glucose-regulated protein (GRP78), which are endoplasmic reticulum (ER) stress markers, in MIN6 cells. On the other hand, astaxanthin attenuated the increased CHOP content, but further up-regulated palmitate-stimulated GRP78 protein expression. By contrast, NAC had no effects on either CHOP or GRP78 enhancement induced by palmitate in MIN6 cells. In conclusion, astaxanthin diminishes the palmitate-stimulated increase in MCP-1 secretion via the downregulation of JNK pathways in MIN6 cells, and affects VEGF120 secretion through PI3K/Akt pathways. Moreover, astaxanthin can prevent not only oxidative stress caused endogenously by palmitate but also ER stress, which NAC fails to attenuate, via upregulation of GRP78, an ER chaperon.
Highlights
Astaxanthin has potent antioxidant activity and is characterized by the basic structure of a carotenoid with keto and hydroxyl groups [1,2]
The intracellular concentration of hydroperoxides, a marker of endogenous oxidative stress, in cells treated with palmitate was augmented 2.7‐fold (p < 0.01; Figure 4A)
Astaxanthin was able to attenuate this upregulation of hydroperoxides by 30% compared with palmitate‐stimulated able to attenuate this upregulation of hydroperoxides by 30% compared with palmitate-stimulated cells (p < 0.01; Figure 4A)
Summary
Astaxanthin has potent antioxidant activity and is characterized by the basic structure of a carotenoid with keto and hydroxyl groups [1,2]. Because of this structure, extension of the conjugated system causes activation of astaxanthin as a radical sponge, and astaxanthin can exert both lipophilic and hydrophilic antioxidant activities. Because astaxanthin reportedly protects pancreatic β-cells of db/db mice from glucotoxicity [11] and resolves chronic inflammation and insulin resistance in adipose tissue [12], there are high expectations about its potential clinical effects. The effects of astaxanthin on free fatty acid-induced inflammation and cellular stress in pancreatic β-cells remain as yet unknown
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