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Autophagy Induced by Tumor Necrosis Factor α Mediates Intrinsic Apoptosis in Trophoblastic Cells

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Abstract

To investigate the interconnection of apoptosis and autophagy in trophoblastic cells, we treated JEG-3 cells with tumor necrosis factor α (TNF-α) after transfecting LC3 or Beclin 1 or calpain small interfering RNA (siRNA), which blocks cleavage of autophagy-related gene 5 (Atg5) into N-terminal truncated Atg5 (tAtg5), a mediator between apoptosis and autophagy, and assessed the changes in LC3-II, caspase 9, caspase 3, and tAtg5. We also assessed the TNF-α-induced changes in LC3-II, caspase 9, and caspase 3 in primary trophoblasts from term placentae after transfecting siRNA for LC3 or Beclin 1. In both types of cells, transfection of LC3 or Beclin 1 siRNA significantly attenuated TNF-α-induced increases in LC3-II and activations of caspase 9 and caspase 3. There was significant abrogation of TNF-α-induced expression of tAtg5 after transfection with LC3 or Beclin 1 siRNA. Moreover, transfection with calpain siRNA significantly decreased TNF-α-induced changes in caspase 3 and caspase 9 in addition to tAtg5 in JEG-3 cells. Our data suggest that TNF-α-induced autophagy mediates intrinsic apoptosis, probably through tAtg5, in trophoblastic cells.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, 135-710, Seoul, Korea

    Hyun-Hwa Cha MD, Hyo-Youn Kim MS, Suk-Joo Choi MD, PhD, Soo-young Oh MD, PhD & Cheong-Rae Roh MD, PhD

  2. Department of Obstetrics and Gynecology, Kyungpook National University Hospital, Kyungpook University School of Medicine, Seoul, Korea

    Hyun-Hwa Cha MD

  3. Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea

    Jae Ryoung Hwang PhD

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  1. Hyun-Hwa Cha MD
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  2. Jae Ryoung Hwang PhD
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  3. Hyo-Youn Kim MS
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  4. Suk-Joo Choi MD, PhD
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  5. Soo-young Oh MD, PhD
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  6. Cheong-Rae Roh MD, PhD
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Correspondence to Cheong-Rae Roh MD, PhD.

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Cha, HH., Hwang, J.R., Kim, HY. et al. Autophagy Induced by Tumor Necrosis Factor α Mediates Intrinsic Apoptosis in Trophoblastic Cells. Reprod. Sci. 21, 612–622 (2014). https://doi.org/10.1177/1933719113508816

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