Limits...
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 cell viability and apoptosis of SH-SY5Y cells. Cells were incubated with various concentrations of acetaldehyde for 24 h. (a) Cell viability was determined with trypan blue assay. The number of cells in control group is set to 100%. (b) The cells were fixed and stained with Hoechst 33258. (c) SH-SY5Y cells were treated with different concentration of acetaldehyde for 24 h. Total RNA was isolated after the treatment and the expression of Bcl-2, Bcl-xL, and Bax genes was assessed by RT-PCR. The expression of GAPDH was used as an internal control. (d) Total lysates of cells were collected and the caspase 3 activities were determined. Data are expressed as the values of concentration of pNA. Values are means ± SD, n = 3. ∗∗, significantly different from untreated cells (P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4663355&req=5

fig1: Effects of acetaldehyde on the cell viability and apoptosis of SH-SY5Y cells. Cells were incubated with various concentrations of acetaldehyde for 24 h. (a) Cell viability was determined with trypan blue assay. The number of cells in control group is set to 100%. (b) The cells were fixed and stained with Hoechst 33258. (c) SH-SY5Y cells were treated with different concentration of acetaldehyde for 24 h. Total RNA was isolated after the treatment and the expression of Bcl-2, Bcl-xL, and Bax genes was assessed by RT-PCR. The expression of GAPDH was used as an internal control. (d) Total lysates of cells were collected and the caspase 3 activities were determined. Data are expressed as the values of concentration of pNA. Values are means ± SD, n = 3. ∗∗, significantly different from untreated cells (P < 0.01).

Mentions: We first examined the effect of acetaldehyde on the cell viability of SH-SY5Y cells. As shown in Figure 1(a), acetaldehyde decreased the viability of SH-SY5Y cells significantly and in a concentration-dependent manner, suggesting that acetaldehyde induced cytotoxicity of SH-SY5Y cells. Hoechst 33528 staining of cells treated with 10 mM of acetaldehyde for 24 h demonstrated that acetaldehyde induced apoptosis of SH-SY5Y cells (Figure 1(b)).


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 cell viability and apoptosis of SH-SY5Y cells. Cells were incubated with various concentrations of acetaldehyde for 24 h. (a) Cell viability was determined with trypan blue assay. The number of cells in control group is set to 100%. (b) The cells were fixed and stained with Hoechst 33258. (c) SH-SY5Y cells were treated with different concentration of acetaldehyde for 24 h. Total RNA was isolated after the treatment and the expression of Bcl-2, Bcl-xL, and Bax genes was assessed by RT-PCR. The expression of GAPDH was used as an internal control. (d) Total lysates of cells were collected and the caspase 3 activities were determined. Data are expressed as the values of concentration of pNA. Values are means ± SD, n = 3. ∗∗, significantly different from untreated cells (P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Effects of acetaldehyde on the cell viability and apoptosis of SH-SY5Y cells. Cells were incubated with various concentrations of acetaldehyde for 24 h. (a) Cell viability was determined with trypan blue assay. The number of cells in control group is set to 100%. (b) The cells were fixed and stained with Hoechst 33258. (c) SH-SY5Y cells were treated with different concentration of acetaldehyde for 24 h. Total RNA was isolated after the treatment and the expression of Bcl-2, Bcl-xL, and Bax genes was assessed by RT-PCR. The expression of GAPDH was used as an internal control. (d) Total lysates of cells were collected and the caspase 3 activities were determined. Data are expressed as the values of concentration of pNA. Values are means ± SD, n = 3. ∗∗, significantly different from untreated cells (P < 0.01).
Mentions: We first examined the effect of acetaldehyde on the cell viability of SH-SY5Y cells. As shown in Figure 1(a), acetaldehyde decreased the viability of SH-SY5Y cells significantly and in a concentration-dependent manner, suggesting that acetaldehyde induced cytotoxicity of SH-SY5Y cells. Hoechst 33528 staining of cells treated with 10 mM of acetaldehyde for 24 h demonstrated that acetaldehyde induced apoptosis of SH-SY5Y cells (Figure 1(b)).

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