title: Autophagy induced by tumor necrosis factor α mediates intrinsic apoptosis in trophoblastic cells.
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.
authors.affiliation: 1Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyun-Hwa
authors.initials: HH
authors.lastname: Cha
authors.forename: Jae Ryoung
authors.initials: JR
authors.lastname: Hwang
authors.forename: Hyo-Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Suk-Joo
authors.initials: SJ
authors.lastname: Choi
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Oh
authors.forename: Cheong-Rae
authors.initials: CR
authors.lastname: Roh
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D014327:Trophoblasts / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Atg5; apoptosis; autophagy; trophoblasts