Limited activation of the intrinsic apoptotic pathway plays a main role in amyloid-β-induced apoptosis without eliciting the activation of the extrinsic apoptotic pathway

  • Authors:
    • Md. Imamul Islam
    • Md. Golam Sharoar
    • Eun-Kyoung Ryu
    • Il-Seon Park
  • View Affiliations

  • Published online on: October 16, 2017     https://doi.org/10.3892/ijmm.2017.3193
  • Pages:1971-1982
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Abstract

Amyloid-β (Aβ), a main pathogenic factor of Alzheimer's disease (AD), induces apoptosis accompanied by caspase activation. However, limited caspase activation and the suppression of the intrinsic apoptotic pathway (IAPW) are frequently observed upon Aβ treatment. In this study, we investigated whether these suppressive effects of Aβ can be overcome; we also examined the death-related pathways. Single treatments of cells with Aβ42 for up to 48 h barely induced caspase activation. In cells treated with Aβ42 twice for 2 h followed by 22 h (2+22 h) or for longer durations, the apoptotic protease activating factor-1 (Apaf-1) apoptosome was formed and caspases-3 and -9 were activated to a certain extent, suggesting the activation of the IAPW. However, the Aβ42-induced activation of the IAPW differed from that induced by treatment with other agents, such as staurosporine (STS) in that lower amounts of cytochrome c were released from the mitochondria, the majority of procaspase-9 in the Apaf-1 complex was not processed and caspase-3 was activated to a lesser extent in the peptide-treated cells. Thus, it seemed that the IAPW was not fully activated by Aβ42. The 30- and 41/43-kDa fragments derived from procaspase-8 were detected, which appear to be produced through the IAPW without death-inducing signaling-complex (DISC) formation, a key feature of the extrinsic apoptotic pathway (EAPW). Bid cleavage was observed only after caspase-3 activity reached its maximal levels, suggesting that the cleavage may contribute in a limited capacity to the amplification process of the IAPW in the Aβ-treated cells. Taken together, our data suggest that the IAPW, albeit functional only to a limited extent, plays a major role in Aβ42-induced apoptosis without the EAPW.

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December 2017
Volume 40 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Islam, M.I., Sharoar, M.G., Ryu, E., & Park, I. (2017). Limited activation of the intrinsic apoptotic pathway plays a main role in amyloid-β-induced apoptosis without eliciting the activation of the extrinsic apoptotic pathway. International Journal of Molecular Medicine, 40, 1971-1982. https://doi.org/10.3892/ijmm.2017.3193
MLA
Islam, M. I., Sharoar, M. G., Ryu, E., Park, I."Limited activation of the intrinsic apoptotic pathway plays a main role in amyloid-β-induced apoptosis without eliciting the activation of the extrinsic apoptotic pathway". International Journal of Molecular Medicine 40.6 (2017): 1971-1982.
Chicago
Islam, M. I., Sharoar, M. G., Ryu, E., Park, I."Limited activation of the intrinsic apoptotic pathway plays a main role in amyloid-β-induced apoptosis without eliciting the activation of the extrinsic apoptotic pathway". International Journal of Molecular Medicine 40, no. 6 (2017): 1971-1982. https://doi.org/10.3892/ijmm.2017.3193