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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

Effects of acetaldehyde treatment on the activation of Akt and CREB in SH-SY5Y cells. SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 h. Total cell lysates were collected and the amount of Akt, phospho-Akt (Ser473) (a), CREB, and phospho-CREB (Ser 133) (b) was determined by Western blot analysis. The intensities of the bands were quantified by densitometric analyses and normalized by the amount of Akt or CREB. Values are means ± SD from three independent experiments. ∗, significantly different from control (P < 0.05); ∗∗, significantly different from control (P < 0.01).
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fig2: Effects of acetaldehyde treatment on the activation of Akt and CREB in SH-SY5Y cells. SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 h. Total cell lysates were collected and the amount of Akt, phospho-Akt (Ser473) (a), CREB, and phospho-CREB (Ser 133) (b) was determined by Western blot analysis. The intensities of the bands were quantified by densitometric analyses and normalized by the amount of Akt or CREB. Values are means ± SD from three independent experiments. ∗, significantly different from control (P < 0.05); ∗∗, significantly different from control (P < 0.01).

Mentions: Akt/CREB pathway is important for the survival of neuronal cells [15]. To find out whether acetaldehyde affects cell survival pathway, the activation of Akt and CREB was examined by Western blot analysis. As shown in Figure 2(a), treatment of acetaldehyde (10 and 25 mM) for 24 h induced a significant decrease in the levels of activated Akt. Similarly, levels of activated CREB were also decreased by the treatment of acetaldehyde (Figure 2(b)). These data suggested that acetaldehyde may decrease cell viability and promote apoptosis by inhibiting the activation of Akt and CREB.


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)

Effects of acetaldehyde treatment on the activation of Akt and CREB in SH-SY5Y cells. SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 h. Total cell lysates were collected and the amount of Akt, phospho-Akt (Ser473) (a), CREB, and phospho-CREB (Ser 133) (b) was determined by Western blot analysis. The intensities of the bands were quantified by densitometric analyses and normalized by the amount of Akt or CREB. Values are means ± SD from three independent experiments. ∗, significantly different from control (P < 0.05); ∗∗, significantly different from control (P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4663355&req=5

fig2: Effects of acetaldehyde treatment on the activation of Akt and CREB in SH-SY5Y cells. SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 h. Total cell lysates were collected and the amount of Akt, phospho-Akt (Ser473) (a), CREB, and phospho-CREB (Ser 133) (b) was determined by Western blot analysis. The intensities of the bands were quantified by densitometric analyses and normalized by the amount of Akt or CREB. Values are means ± SD from three independent experiments. ∗, significantly different from control (P < 0.05); ∗∗, significantly different from control (P < 0.01).
Mentions: Akt/CREB pathway is important for the survival of neuronal cells [15]. To find out whether acetaldehyde affects cell survival pathway, the activation of Akt and CREB was examined by Western blot analysis. As shown in Figure 2(a), treatment of acetaldehyde (10 and 25 mM) for 24 h induced a significant decrease in the levels of activated Akt. Similarly, levels of activated CREB were also decreased by the treatment of acetaldehyde (Figure 2(b)). These data suggested that acetaldehyde may decrease cell viability and promote apoptosis by inhibiting the activation of Akt and CREB.

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