Astaxanthin Inhibits Acetaldehyde-Induced Cytotoxicity in SH-SY5Y Cells by Modulating Akt/CREB and p38MAPK/ERK Signaling Pathways.

Tingting Yan,Xiaotong Lin,Xia Zhang,Yan Zhao

doi:10.3390/md14030056

Tingting Yan, Xiaotong Lin + Show 2 more

Open Access

https://doi.org/10.3390/md14030056

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Journal: Marine Drugs	Publication Date: Mar 10, 2016
Citations: 84	License type: CC BY 4.0

Affiliation: Harbin Institute of Technology

Abstract

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.

Highlights

Chronic overuse of alcohol can lead to brain tissue damage and cognitive dysfunction [1].Studies have shown that heavy drinking is associated with increased risk and earlier onset of dementia such as Alzheimer’s disease [2,3]
The results suggest that astaxanthin treatment may be beneficial for preventing neurotoxicity associated with acetaldehyde and excessive alcohol consumption
It has been shown that acetaldehyde induces cytotoxicity in rat cerebellar primary neuronal cultures in a dose dependent manner [12]

Summary

Introduction

Chronic overuse of alcohol can lead to brain tissue damage and cognitive dysfunction [1]. Studies have shown that heavy drinking is associated with increased risk and earlier onset of dementia such as Alzheimer’s disease [2,3]. Ethanol is metabolized to acetaldehyde following consumption by alcohol dehydrogenase (ADH). Catalase and cytochrome p450 2E1 are additional enzymes that are critical for the local formation of acetaldehyde [4]. Acetaldehyde is further oxidized to acetate by aldehyde dehydrogenase (ALDH) 2. The level of acetaldehyde in blood elevates upon overconsumption of alcohol. Individuals with defective ALDH2 have much higher blood acetaldehyde levels after drinking alcohol in comparison with normal individuals [5]

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