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Protective effects of astragaloside IV against amyloid beta1-42 neurotoxicity by inhibiting the mitochondrial permeability transition pore opening.

Sun Q, Jia N, Wang W, Jin H, Xu J, Hu H - PLoS ONE (2014)

Bottom Line: The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aβ1-42.Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment.These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Anatomy and Histo-Embryology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.

ABSTRACT
Mitochondrial dysfunction caused by amyloid β-peptide (Aβ) plays an important role in the pathogenesis of Alzheimer disease (AD). Substantial evidence has indicated that the mitochondrial permeability transition pore (mPTP) opening is involved in Aβ-induced neuronal death and reactive oxygen species (ROS) generation. Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus, has been reported as an effective anti-oxidant for treating neurodegenerative diseases. However, the molecular mechanisms still need to be clarified. In this study, we investigated whether AS-IV could prevent Aβ1-42-induced neurotoxicity in SK-N-SH cells via inhibiting the mPTP opening. The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aβ1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (ΔΨm), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aβ1-42 rich milieu. Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment. These data indicate that AS-IV prevents Aβ1-42-induced SK-N-SH cell apoptosis via inhibiting the mPTP opening and ROS generation. These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.

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AS-IV inhibited Aβ1-42-induced increase of Bax/Bcl-2 ratio.(A) Western blot results of AS-IV on expression of Bax and Bcl-2. (B) The quantification of immunoreactive bands for Bax and Bcl-2 relative to β-actin and the Bax/Bcl-2 ratio was determined. #P<0.01 vs vehicle; *P<0.01 vs Aβ1-42 (n = 4).
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pone-0098866-g008: AS-IV inhibited Aβ1-42-induced increase of Bax/Bcl-2 ratio.(A) Western blot results of AS-IV on expression of Bax and Bcl-2. (B) The quantification of immunoreactive bands for Bax and Bcl-2 relative to β-actin and the Bax/Bcl-2 ratio was determined. #P<0.01 vs vehicle; *P<0.01 vs Aβ1-42 (n = 4).

Mentions: The Bcl-2 family proteins are associated with apoptosis. In this study, we examined the expression of Bax and Bcl-2 by Western blot. Compared with the vehicle group, the Aβ1-42 group displayed lower expression of Bcl-2 and higher expression of Bax. The ratio of Bax/Bcl-2 in the Aβ1-42 group was significantly increased (P<0.01). Cells pretreated with AS-IV at 25 or 50 µM showed reversed ratios of Bax and Bcl-2 compared with cells in the Aβ1-42 group. The ratio of Bax/Bcl-2 in the AS-IV pretreated group was decreased compared with the Aβ1-42 group (P<0.01). No difference was observed between pretreatment of 10 µM AS-IV and Aβ1-42 treatment alone. 50 µM AS-IV alone treatment did not show an insult to SK-N-SH cells (Fig 8A, B).


Protective effects of astragaloside IV against amyloid beta1-42 neurotoxicity by inhibiting the mitochondrial permeability transition pore opening.

Sun Q, Jia N, Wang W, Jin H, Xu J, Hu H - PLoS ONE (2014)

AS-IV inhibited Aβ1-42-induced increase of Bax/Bcl-2 ratio.(A) Western blot results of AS-IV on expression of Bax and Bcl-2. (B) The quantification of immunoreactive bands for Bax and Bcl-2 relative to β-actin and the Bax/Bcl-2 ratio was determined. #P<0.01 vs vehicle; *P<0.01 vs Aβ1-42 (n = 4).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4048237&req=5

pone-0098866-g008: AS-IV inhibited Aβ1-42-induced increase of Bax/Bcl-2 ratio.(A) Western blot results of AS-IV on expression of Bax and Bcl-2. (B) The quantification of immunoreactive bands for Bax and Bcl-2 relative to β-actin and the Bax/Bcl-2 ratio was determined. #P<0.01 vs vehicle; *P<0.01 vs Aβ1-42 (n = 4).
Mentions: The Bcl-2 family proteins are associated with apoptosis. In this study, we examined the expression of Bax and Bcl-2 by Western blot. Compared with the vehicle group, the Aβ1-42 group displayed lower expression of Bcl-2 and higher expression of Bax. The ratio of Bax/Bcl-2 in the Aβ1-42 group was significantly increased (P<0.01). Cells pretreated with AS-IV at 25 or 50 µM showed reversed ratios of Bax and Bcl-2 compared with cells in the Aβ1-42 group. The ratio of Bax/Bcl-2 in the AS-IV pretreated group was decreased compared with the Aβ1-42 group (P<0.01). No difference was observed between pretreatment of 10 µM AS-IV and Aβ1-42 treatment alone. 50 µM AS-IV alone treatment did not show an insult to SK-N-SH cells (Fig 8A, B).

Bottom Line: The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aβ1-42.Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment.These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Anatomy and Histo-Embryology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.

ABSTRACT
Mitochondrial dysfunction caused by amyloid β-peptide (Aβ) plays an important role in the pathogenesis of Alzheimer disease (AD). Substantial evidence has indicated that the mitochondrial permeability transition pore (mPTP) opening is involved in Aβ-induced neuronal death and reactive oxygen species (ROS) generation. Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus, has been reported as an effective anti-oxidant for treating neurodegenerative diseases. However, the molecular mechanisms still need to be clarified. In this study, we investigated whether AS-IV could prevent Aβ1-42-induced neurotoxicity in SK-N-SH cells via inhibiting the mPTP opening. The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aβ1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (ΔΨm), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aβ1-42 rich milieu. Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment. These data indicate that AS-IV prevents Aβ1-42-induced SK-N-SH cell apoptosis via inhibiting the mPTP opening and ROS generation. These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.

Show MeSH
Related in: MedlinePlus