title: Response of HEK293 and CHO cells overexpressing fusiogenic syncytin-1 to mitochondrion-mediated apoptosis induced by antimycin A.
abstract: Apoptosis is essential for the regulation of cellular homeostasis in the placenta and is also involved in the pathophysiology of pregnancy-related diseases such as pre-eclampsia and intrauterine growth restriction (IUGR). Syncytin-1, a fusiogenic glycoprotein of endogenous-retroviral origin expressed in human trophoblasts, facilitates placental syncytium formation and is found reduced in pre-eclamptic placentas. We focus here on the mitochondrial apoptotic pathway and investigate whether the overexpression of syncytin-1 in HEK293-52 (human embryonic kidney cells) and CHO-52 cells influences the apoptotic response to the mitochondrial inhibitor antimycin A (AA). After the induction of apoptosis by 5 microM AA and incubation for up to 36 h in the absence of serum, the mean apoptotic rate was reduced by 15-30% in syncytin-1 transfected cells compared with mock-transfectants. After 12 h of challenge with AA we found lower cytochrome c levels in the cytoplasmic protein fraction and higher amounts in the mitochondrial fraction in syncytin-1 transfectants compared with mock-transfectants. We observed a decreased Mitotracker Red staining of mitochondria following AA challenge for 24 h in mock-treated CHO cells, in particular, compared with syncytin-1 transfectants. Moreover, we found a reduced activation of caspase 9 in syncytin-1 transfected HEK293-52 cells after 48 h of apoptotic challenge compared to mock-transfectants. However, a high expression of anti-apoptotic Bcl-x(L) was found in both cell types. Using syncytin-1 transfected HEK293-52 cells and CHO-52 cells, we provide initial evidence that syncytin-1 may exert its anti-apoptotic function at the mitochondrial level. A reduced release of cytochrome c followed by a diminished activation of caspase 9 is a possible mechanism.
authors: Children's and Adolescents' Hospital, University of Erlangen-Nuremberg, Erlangen, Germany. ina.knerr@uk-erlangen.de
authors: Ina
authors: I
authors: Knerr
authors: Stephan
authors: S
authors: Söder
authors: Elke
authors: E
authors: Licha
authors: Thomas
authors: T
authors: Aigner
authors: Wolfgang
authors: W
authors: Rascher
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D053453:Caspase 9 / Q000378:metabolism; D002459:Cell Fusion; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D015686:Gene Products, env / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin; D000968:Antimycin A; D053453:Caspase 9