Astaxanthin Inhibits Acetaldehyde-Induced Cytotoxicity in SH-SY5Y Cells by Modulating Akt/CREB and p38MAPK/ERK Signaling Pathways.
Astaxanthin Inhibits Acetaldehyde-Induced Cytotoxicity in SH-SY5Y Cells by Modulating Akt/CREB and p38MAPK/ERK Signaling Pathways.
复制标题
虾青素通过调节 Akt/CREB 和 p38MAPK/ERK 信号通路抑制 SH-SY5Y 细胞中乙醛诱导的细胞毒性
DOI：
10.3390/md14030056
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发表时间：
2016-03-10
期刊：
影响因子：
5.4
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Yan T;Zhao Y;Zhang X;Lin X
过量饮酒会导致脑组织损伤和认知功能障碍。乙醛是乙醇毒性最强的代谢产物，可介导慢性过量饮酒引起的脑组织损伤和认知功能障碍。在这项研究中，虾青素，海洋生物活性化合物，对乙酰氨基酚诱导的细胞毒作用的SH-SY 5 Y细胞的影响进行了研究。研究发现，虾青素通过改善乙醛对Bcl-2家族蛋白表达的影响，阻止乙醛诱导的抗凋亡蛋白Bcl-2的减少和促凋亡蛋白巴克的增加，从而保护细胞免于凋亡。进一步的分析表明，虾青素治疗抑制乙酰丙酮酸诱导的激活Akt和环AMP反应元件结合蛋白（CREB）的水平的降低。虾青素处理还防止了乙酰丙酮酸诱导的活化的p38丝裂原活化蛋白激酶（MAPK）水平的增加和活化的细胞外信号调节激酶（ERK）水平的降低。Akt/CREB通路的激活促进细胞存活并参与Bcl-2基因的上调。P38 MAPK在细胞凋亡中起重要作用，而ERK介导细胞凋亡的抑制。因此，虾青素可能通过促进Akt/CREB和ERK的激活，阻断p38 MAPK的激活，从而抑制乙酰丙酮诱导的细胞凋亡。此外，虾青素处理抑制乙醛诱导的氧化应激，恢复SH-SY 5 Y细胞的抗氧化能力。因此，虾青素可能通过维持氧化还原平衡和调节凋亡和存活信号来保护细胞免受乙酰丙酮诱导的细胞毒性。结果表明，虾青素治疗可能有利于预防与乙醛和过量饮酒相关的神经毒性。
Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. Acetaldehyde, the most toxic metabolite of ethanol, mediates the brain tissue damage and cognitive dysfunction induced by chronic excessive alcohol consumption. In this study, the effect of astaxanthin, a marine bioactive compound, on acetaldehyde-induced cytotoxicity was investigated in SH-SY5Y cells. It was found that astaxanthin protected cells from apoptosis by ameliorating the effect of acetaldehyde on the expression of Bcl-2 family proteins, preventing the reduction of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bak induced by acetaldehyde. Further analyses showed that astaxanthin treatment inhibited acetaldehyde-induced reduction of the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). Astaxanthin treatment also prevented acetaldehyde-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK) and decrease of the level of activated extracellular signal-regulated kinases (ERKs). Activation of Akt/CREB pathway promotes cell survival and is involved in the upregulation of Bcl-2 gene. P38MAPK plays a critical role in apoptotic events while ERKs mediates the inhibition of apoptosis. Thus, astaxanthin may inhibit acetaldehyde-induced apoptosis through promoting the activation of Akt/CREB and ERKs and blocking the activation of p38MAPK. In addition, astaxanthin treatment suppressed the oxidative stress induced by acetaldehyde and restored the antioxidative capacity of SH-SY5Y cells. Therefore, astaxanthin may protect cells against acetaldehyde-induced cytotoxicity through maintaining redox balance and modulating apoptotic and survival signals. The results suggest that astaxanthin treatment may be beneficial for preventing neurotoxicity associated with acetaldehyde and excessive alcohol consumption.