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Moderate activation of autophagy regulates the intracellular calcium ion concentration and mitochondrial membrane potential in beta-amyloid-treated PC12 cells.
Neurosci Lett. 2016 Apr 08; 618:50-57.NL

Abstract

Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease. Aggregated beta-amyloid (Aβ) disturbs Ca(2+) homeostasis and causes mitochondrial dysfunction and finally underlies AD. Recent evidence suggests that autophagy initiation by Beclin-1 protein might be involved in the pathogenesis of AD. However, the effects of Beclin-1 dependent autophagy on intracellular calcium ion concentration ([Ca(2+)]i) and mitochondrial membrane potential (MMP) is unclear. The effects of Beclin-1 dependent autophagy that were activated by a gradient concentration of autophagy activator rapamycin or inhibited by autophagy inhibitor 3-methyladenine (3-MA) on cell viability and cell morphology were examined. Pretreatment with rapamycin significantly up-regulated the expression of Beclin-1 in response to Aβ1-42 application, but after pretreatment with 3-MA it was significantly down-regulated. Moderate activation of Beclin-1 dependent autophagy had an up regulation effect on cell viability and could maintain the original morphology of cells. Furthermore, rapamycin or 3-MA on [Ca(2+)]i and MMP in Aβ1-42 treatment of PC12 cells were evaluated. We also report that PC12 cells treated with Aβ1-42 showed an increase in [Ca(2+)]i but a decrease in MMP when compared to the normal control. However the application of rapamycin prior to this prevented the increase in [Ca(2+)]i and the decrease in MMP in response to Aβ1-42. When 3-MA was applied this exacerbated the effect of Aβ1-42 on the [Ca(2+)]i and the MMP. This shows that moderate activation of Beclin-1 dependent autophagy by rapamycin can modulate Ca(2+) homeostasis and maintain MMP in response to Aβ1-42 induced cytotoxicity and so may have a preventive function in AD.

Authors+Show Affiliations

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Sanya Hospital of Traditional Chinese Medicine, Sanya, China.The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Hainan Tropical Ocean University, Sanya, China.The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: fangyq2@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26923671

Citation

Xue, Zhongfeng, et al. "Moderate Activation of Autophagy Regulates the Intracellular Calcium Ion Concentration and Mitochondrial Membrane Potential in Beta-amyloid-treated PC12 Cells." Neuroscience Letters, vol. 618, 2016, pp. 50-57.
Xue Z, Guo Y, Fang Y. Moderate activation of autophagy regulates the intracellular calcium ion concentration and mitochondrial membrane potential in beta-amyloid-treated PC12 cells. Neurosci Lett. 2016;618:50-57.
Xue, Z., Guo, Y., & Fang, Y. (2016). Moderate activation of autophagy regulates the intracellular calcium ion concentration and mitochondrial membrane potential in beta-amyloid-treated PC12 cells. Neuroscience Letters, 618, 50-57. https://doi.org/10.1016/j.neulet.2016.02.044
Xue Z, Guo Y, Fang Y. Moderate Activation of Autophagy Regulates the Intracellular Calcium Ion Concentration and Mitochondrial Membrane Potential in Beta-amyloid-treated PC12 Cells. Neurosci Lett. 2016 Apr 8;618:50-57. PubMed PMID: 26923671.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Moderate activation of autophagy regulates the intracellular calcium ion concentration and mitochondrial membrane potential in beta-amyloid-treated PC12 cells. AU - Xue,Zhongfeng, AU - Guo,Yalei, AU - Fang,Yongqi, Y1 - 2016/02/26/ PY - 2016/01/15/received PY - 2016/02/18/revised PY - 2016/02/23/accepted PY - 2016/3/1/entrez PY - 2016/3/1/pubmed PY - 2016/8/23/medline KW - Alzheimer’s disease KW - Autophagy KW - Beclin-1 KW - Beta-amyloid KW - Intracellular calcium KW - Mitochondrial membrane potential SP - 50 EP - 57 JF - Neuroscience letters JO - Neurosci Lett VL - 618 N2 - Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease. Aggregated beta-amyloid (Aβ) disturbs Ca(2+) homeostasis and causes mitochondrial dysfunction and finally underlies AD. Recent evidence suggests that autophagy initiation by Beclin-1 protein might be involved in the pathogenesis of AD. However, the effects of Beclin-1 dependent autophagy on intracellular calcium ion concentration ([Ca(2+)]i) and mitochondrial membrane potential (MMP) is unclear. The effects of Beclin-1 dependent autophagy that were activated by a gradient concentration of autophagy activator rapamycin or inhibited by autophagy inhibitor 3-methyladenine (3-MA) on cell viability and cell morphology were examined. Pretreatment with rapamycin significantly up-regulated the expression of Beclin-1 in response to Aβ1-42 application, but after pretreatment with 3-MA it was significantly down-regulated. Moderate activation of Beclin-1 dependent autophagy had an up regulation effect on cell viability and could maintain the original morphology of cells. Furthermore, rapamycin or 3-MA on [Ca(2+)]i and MMP in Aβ1-42 treatment of PC12 cells were evaluated. We also report that PC12 cells treated with Aβ1-42 showed an increase in [Ca(2+)]i but a decrease in MMP when compared to the normal control. However the application of rapamycin prior to this prevented the increase in [Ca(2+)]i and the decrease in MMP in response to Aβ1-42. When 3-MA was applied this exacerbated the effect of Aβ1-42 on the [Ca(2+)]i and the MMP. This shows that moderate activation of Beclin-1 dependent autophagy by rapamycin can modulate Ca(2+) homeostasis and maintain MMP in response to Aβ1-42 induced cytotoxicity and so may have a preventive function in AD. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/26923671/Moderate_activation_of_autophagy_regulates_the_intracellular_calcium_ion_concentration_and_mitochondrial_membrane_potential_in_beta_amyloid_treated_PC12_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(16)30110-0 DB - PRIME DP - Unbound Medicine ER -