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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 on the activation of p38MAPK/ERK/JNK in SH-SY5Y cells. SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 h. Total cell lysates were collected and the protein levels of p38MAPK, phosho-p38MAPK (Thr180/Tyr182) (a), ERK (p44/p42) MAPK and phospho-ERK (Thr202/Tyr204) (b), and JNK and phospho-JNK (Thr183/Tyr185) (c) were determined by Western blot analyses. The intensities of the bands were quantified by densitometric analyses and normalized by the amount of p38MAPK, JNK, or ERK. 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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fig3: Effects of acetaldehyde on the activation of p38MAPK/ERK/JNK in SH-SY5Y cells. SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 h. Total cell lysates were collected and the protein levels of p38MAPK, phosho-p38MAPK (Thr180/Tyr182) (a), ERK (p44/p42) MAPK and phospho-ERK (Thr202/Tyr204) (b), and JNK and phospho-JNK (Thr183/Tyr185) (c) were determined by Western blot analyses. The intensities of the bands were quantified by densitometric analyses and normalized by the amount of p38MAPK, JNK, or ERK. Values are means ± SD from three independent experiments. ∗, significantly different from control (P < 0.05); ∗∗, significantly different from control (P < 0.01).

Mentions: MAPKs have been shown to have important roles in promotion or inhibition of apoptosis. We next examined the effect of acetaldehyde on the activation of p38MAPK/ERK/JNK pathway by Western blot analysis. Treatment of acetaldehyde increased the levels of activated p38MAPK in a dose-dependent manner (Figure 3(a)). In contrast, acetaldehyde treatment caused a downregulation of the levels of activated ERK (Figure 3(b)). There was only a slight change in the activation of JNK after 24 h treatment of acetaldehyde (Figure 3(c)).


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 on the activation of p38MAPK/ERK/JNK in SH-SY5Y cells. SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 h. Total cell lysates were collected and the protein levels of p38MAPK, phosho-p38MAPK (Thr180/Tyr182) (a), ERK (p44/p42) MAPK and phospho-ERK (Thr202/Tyr204) (b), and JNK and phospho-JNK (Thr183/Tyr185) (c) were determined by Western blot analyses. The intensities of the bands were quantified by densitometric analyses and normalized by the amount of p38MAPK, JNK, or ERK. 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

Show All Figures
getmorefigures.php?uid=PMC4663355&req=5

fig3: Effects of acetaldehyde on the activation of p38MAPK/ERK/JNK in SH-SY5Y cells. SH-SY5Y cells were treated with different concentrations of acetaldehyde for 24 h. Total cell lysates were collected and the protein levels of p38MAPK, phosho-p38MAPK (Thr180/Tyr182) (a), ERK (p44/p42) MAPK and phospho-ERK (Thr202/Tyr204) (b), and JNK and phospho-JNK (Thr183/Tyr185) (c) were determined by Western blot analyses. The intensities of the bands were quantified by densitometric analyses and normalized by the amount of p38MAPK, JNK, or ERK. Values are means ± SD from three independent experiments. ∗, significantly different from control (P < 0.05); ∗∗, significantly different from control (P < 0.01).
Mentions: MAPKs have been shown to have important roles in promotion or inhibition of apoptosis. We next examined the effect of acetaldehyde on the activation of p38MAPK/ERK/JNK pathway by Western blot analysis. Treatment of acetaldehyde increased the levels of activated p38MAPK in a dose-dependent manner (Figure 3(a)). In contrast, acetaldehyde treatment caused a downregulation of the levels of activated ERK (Figure 3(b)). There was only a slight change in the activation of JNK after 24 h treatment of acetaldehyde (Figure 3(c)).

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