Yan Tingting, Zhao Yan, Zhang Xia, Lin Xiaotong
Department of Bioengineering, Harbin Institute of Technology, Weihai 264209, Shandong, China.
Mar Drugs. 2016 Mar 10;14(3):56. doi: 10.3390/md14030056.
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.
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，介导慢性过量饮酒所致的脑组织损伤和认知功能障碍。在本研究中，我们在SH-SY5Y细胞中研究了海洋生物活性化合物虾青素对乙醛诱导的细胞毒性的影响。结果发现，虾青素通过改善乙醛对Bcl-2家族蛋白表达的影响来保护细胞免受凋亡，防止乙醛诱导的抗凋亡蛋白Bcl-2减少和促凋亡蛋白Bak增加。进一步分析表明，虾青素处理可抑制乙醛诱导的活化Akt和环磷酸腺苷反应元件结合蛋白（CREB）水平降低。虾青素处理还可防止乙醛诱导的活化p38丝裂原活化蛋白激酶（MAPK）水平升高和活化细胞外信号调节激酶（ERK）水平降低。Akt/CREB通路的激活促进细胞存活，并参与Bcl-2基因的上调。P38MAPK在凋亡事件中起关键作用，而ERK介导对凋亡的抑制。因此，虾青素可能通过促进Akt/CREB和ERK的激活以及阻断p38MAPK的激活来抑制乙醛诱导的凋亡。此外，虾青素处理可抑制乙醛诱导的氧化应激，并恢复SH-SY5Y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以及调节凋亡和存活信号来保护细胞免受乙醛诱导的细胞毒性。结果表明，虾青素处理可能有助于预防与乙醛和过量饮酒相关的神经毒性。
