Autophagy Induced by Tumor Necrosis Factor α Mediates Intrinsic Apoptosis in Trophoblastic Cells. (May 2014)

• Record Type: Journal Article
• Authors: Cha, Hyun-Hwa; Hwang, Jae Ryoung; Kim, Hyo-Youn; Choi, Suk-Joo; Oh, Soo-young; Roh, Cheong-Rae
• Is Part Of: Reproductive sciences. Volume 21:Number 5(2014:May)
• Page Start: 612
• Page End: 622
• Publication Date: 2014-05
• Subjects: apoptosis -- Atg5 -- autophagy -- trophoblasts; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719113508816
• Languages: English
• ISSNs: 1933-7191

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.