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Autophagy induced by tumor necrosis factor α mediates intrinsic apoptosis in trophoblastic cells

Hyun-Hwa Cha1, Jae Ryoung Hwang, Hyo-Youn Kim

  • 11Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Reproductive Sciences (Thousand Oaks, Calif.)
|November 8, 2013
PubMed

Insights

Tumor necrosis factor alpha (TNF-α) triggers autophagy that mediates apoptosis in trophoblastic cells, likely via truncated autophagy-related gene 5 (tAtg5). This study reveals a key link between these cellular processes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Reproductive Biology

Background:

  • Apoptosis and autophagy are critical cellular processes.
  • The interplay between apoptosis and autophagy in trophoblastic cells remains incompletely understood.
  • Tumor necrosis factor alpha (TNF-α) is implicated in various cellular functions, including apoptosis and autophagy.

Purpose of the Study:

  • To investigate the interconnection between apoptosis and autophagy in trophoblastic cells.
  • To elucidate the role of autophagy-related gene 5 (Atg5) cleavage in mediating TNF-α-induced cell death.
  • To determine the involvement of autophagy in TNF-α-induced intrinsic apoptosis in trophoblasts.

Main Methods:

  • JEG-3 cells and primary human trophoblasts were treated with TNF-α.
  • Small interfering RNA (siRNA) targeting LC3, Beclin 1, or calpain was used to modulate autophagy and apoptosis-related proteins.
  • Levels of LC3-II, cleaved caspase 9, cleaved caspase 3, and truncated Atg5 (tAtg5) were assessed.

Main Results:

  • Silencing LC3 or Beclin 1 significantly attenuated TNF-α-induced increases in LC3-II and caspase activations.
  • TNF-α-induced expression of tAtg5 was abrogated by LC3 or Beclin 1 siRNA.
  • Calpain siRNA transfection decreased TNF-α-induced caspase changes and tAtg5 expression.

Conclusions:

  • TNF-α-induced autophagy mediates intrinsic apoptosis in trophoblastic cells.
  • The cleavage of Atg5 into tAtg5 appears to be a crucial mediator in this process.
  • Targeting autophagy pathways may offer therapeutic strategies for conditions involving trophoblast dysfunction.
Keywords:
Atg5apoptosisautophagytrophoblasts

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