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Acetaldehyde Induces Cytotoxicity of SH-SY5Y Cells via Inhibition of Akt Activation and Induction of Oxidative Stress.

Yan T, Zhao Y, Zhang X - Oxid Med Cell Longev (2015)

Bottom Line: It has been shown that heavy drinking is associated with an earlier onset of neurodegenerative diseases such as Alzheimer's disease.Acetaldehyde treatment led to a significant decrease in the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB).Therefore, acetaldehyde induces cytotoxicity of SH-SY5Y cells via promotion of apoptotic signaling, inhibition of cell survival pathway, and induction of oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, Harbin Institute of Technology, Weihai, Shandong 264209, China.

ABSTRACT
Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. It has been shown that heavy drinking is associated with an earlier onset of neurodegenerative diseases such as Alzheimer's disease. Acetaldehyde, the most toxic metabolite of ethanol, is speculated to mediate the brain tissue damage and cognitive dysfunction induced by the chronic excessive consumption of alcohol. However, the exact mechanisms by which acetaldehyde induces neurotoxicity are not totally understood. In this study, we investigated the cytotoxic effects of acetaldehyde in SH-SY5Y cells and found that acetaldehyde induced apoptosis of SH-SY5Y cells by downregulating the expression of antiapoptotic Bcl-2 and Bcl-xL and upregulating the expression of proapoptotic Bax. Acetaldehyde treatment led to a significant decrease in the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). In addition, acetaldehyde induced the activation of p38 mitogen-activated protein kinase (MAPK) while inhibiting the activation of extracellular signal-regulated kinases (ERKs, p44/p42MAPK). Meanwhile, acetaldehyde treatment caused an increase in the production of reactive oxygen species and elevated the oxidative stress in SH-SY5Y cells. Therefore, acetaldehyde induces cytotoxicity of SH-SY5Y cells via promotion of apoptotic signaling, inhibition of cell survival pathway, and induction of oxidative stress.

No MeSH data available.


Related in: MedlinePlus

Acetaldehyde increases oxidative stress in SH-SY5Y cells. (a) SH-SY5Y cells were treated with 10 mM of acetaldehyde for 1 h. Cells were then stained with DCFH-DA to determine the production of ROS. Images on the left side are the phase images of the cells. (b) SH-SY5Y cells were treated with 5 mM of acetaldehyde for 2 h. The levels of reduced GSH were determined in the cell lysates. (c) SH-SY5Y cells were treated with different concentration of acetaldehyde for 24 h. MDA production was measured in the cell lysates. Values are means ± SD. ∗, significantly different from control cells (P < 0.05); ∗∗, significantly different from control cells (P < 0.01).
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fig4: Acetaldehyde increases oxidative stress in SH-SY5Y cells. (a) SH-SY5Y cells were treated with 10 mM of acetaldehyde for 1 h. Cells were then stained with DCFH-DA to determine the production of ROS. Images on the left side are the phase images of the cells. (b) SH-SY5Y cells were treated with 5 mM of acetaldehyde for 2 h. The levels of reduced GSH were determined in the cell lysates. (c) SH-SY5Y cells were treated with different concentration of acetaldehyde for 24 h. MDA production was measured in the cell lysates. Values are means ± SD. ∗, significantly different from control cells (P < 0.05); ∗∗, significantly different from control cells (P < 0.01).

Mentions: To further study the underlying mechanism of the cytotoxic effects of acetaldehyde, the effects of acetaldehyde on the redox status of the cells were studied. As shown in Figure 4(a), exposure of acetaldehyde caused a quick and dramatic increase in the production of ROS in SH-SY5Y cells. In addition, acetaldehyde treatment also induced a decrease in the concentration of tripeptide GSH (Figure 4(b)), which plays important function in the detoxification of ROS. MDA, which is a breakdown product of the oxidative degradation of cell membrane lipids, is generally considered as the marker of intracellular oxidative stress and an indicator of lipid peroxidation [16]. Thus, we next determined the concentration of MDA in acetaldehyde treated SH-SY5Y cells. As shown in Figure 4(c), MDA levels increased significantly by acetaldehyde treatment in a concentration-dependent manner. The increase of ROS and MDA levels and the decreased GSH concentration suggested that the oxidative stress was induced by the acetaldehyde treatment, which might subsequently lead to the cytotoxicity and apoptosis of SH-SY5Y cells.


Acetaldehyde Induces Cytotoxicity of SH-SY5Y Cells via Inhibition of Akt Activation and Induction of Oxidative Stress.

Yan T, Zhao Y, Zhang X - Oxid Med Cell Longev (2015)

Acetaldehyde increases oxidative stress in SH-SY5Y cells. (a) SH-SY5Y cells were treated with 10 mM of acetaldehyde for 1 h. Cells were then stained with DCFH-DA to determine the production of ROS. Images on the left side are the phase images of the cells. (b) SH-SY5Y cells were treated with 5 mM of acetaldehyde for 2 h. The levels of reduced GSH were determined in the cell lysates. (c) SH-SY5Y cells were treated with different concentration of acetaldehyde for 24 h. MDA production was measured in the cell lysates. Values are means ± SD. ∗, significantly different from control cells (P < 0.05); ∗∗, significantly different from control cells (P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: Acetaldehyde increases oxidative stress in SH-SY5Y cells. (a) SH-SY5Y cells were treated with 10 mM of acetaldehyde for 1 h. Cells were then stained with DCFH-DA to determine the production of ROS. Images on the left side are the phase images of the cells. (b) SH-SY5Y cells were treated with 5 mM of acetaldehyde for 2 h. The levels of reduced GSH were determined in the cell lysates. (c) SH-SY5Y cells were treated with different concentration of acetaldehyde for 24 h. MDA production was measured in the cell lysates. Values are means ± SD. ∗, significantly different from control cells (P < 0.05); ∗∗, significantly different from control cells (P < 0.01).
Mentions: To further study the underlying mechanism of the cytotoxic effects of acetaldehyde, the effects of acetaldehyde on the redox status of the cells were studied. As shown in Figure 4(a), exposure of acetaldehyde caused a quick and dramatic increase in the production of ROS in SH-SY5Y cells. In addition, acetaldehyde treatment also induced a decrease in the concentration of tripeptide GSH (Figure 4(b)), which plays important function in the detoxification of ROS. MDA, which is a breakdown product of the oxidative degradation of cell membrane lipids, is generally considered as the marker of intracellular oxidative stress and an indicator of lipid peroxidation [16]. Thus, we next determined the concentration of MDA in acetaldehyde treated SH-SY5Y cells. As shown in Figure 4(c), MDA levels increased significantly by acetaldehyde treatment in a concentration-dependent manner. The increase of ROS and MDA levels and the decreased GSH concentration suggested that the oxidative stress was induced by the acetaldehyde treatment, which might subsequently lead to the cytotoxicity and apoptosis of SH-SY5Y cells.

Bottom Line: It has been shown that heavy drinking is associated with an earlier onset of neurodegenerative diseases such as Alzheimer's disease.Acetaldehyde treatment led to a significant decrease in the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB).Therefore, acetaldehyde induces cytotoxicity of SH-SY5Y cells via promotion of apoptotic signaling, inhibition of cell survival pathway, and induction of oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, Harbin Institute of Technology, Weihai, Shandong 264209, China.

ABSTRACT
Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. It has been shown that heavy drinking is associated with an earlier onset of neurodegenerative diseases such as Alzheimer's disease. Acetaldehyde, the most toxic metabolite of ethanol, is speculated to mediate the brain tissue damage and cognitive dysfunction induced by the chronic excessive consumption of alcohol. However, the exact mechanisms by which acetaldehyde induces neurotoxicity are not totally understood. In this study, we investigated the cytotoxic effects of acetaldehyde in SH-SY5Y cells and found that acetaldehyde induced apoptosis of SH-SY5Y cells by downregulating the expression of antiapoptotic Bcl-2 and Bcl-xL and upregulating the expression of proapoptotic Bax. Acetaldehyde treatment led to a significant decrease in the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). In addition, acetaldehyde induced the activation of p38 mitogen-activated protein kinase (MAPK) while inhibiting the activation of extracellular signal-regulated kinases (ERKs, p44/p42MAPK). Meanwhile, acetaldehyde treatment caused an increase in the production of reactive oxygen species and elevated the oxidative stress in SH-SY5Y cells. Therefore, acetaldehyde induces cytotoxicity of SH-SY5Y cells via promotion of apoptotic signaling, inhibition of cell survival pathway, and induction of oxidative stress.

No MeSH data available.


Related in: MedlinePlus