title: Heme-mediated apoptosis and fusion damage in BeWo trophoblast cells.
abstract: Placental malaria (PM) is a complication associated with malaria infection during pregnancy that often leads to abortion, premature delivery, intrauterine growth restriction and low birth weight. Increased levels of circulating free heme, a by-product of Plasmodium-damaged erythrocytes, is a major contributor to inflammation, tissue damage and loss of blood brain barrier integrity associated with fatal experimental cerebral malaria. However, the role of heme in PM remains unknown. Proliferation and apoptosis of trophoblasts and fusion of the mononucleated state to the syncytial state are of major importance to a successful pregnancy. In the present study, we examined the effects of heme on the viability and fusion of a trophoblast-derived cell line (BeWo). Results indicate that heme induces apoptosis in BeWo cells by activation of the STAT3/caspase-3/PARP signaling pathway. In the presence of forskolin, which triggers trophoblast fusion, heme inhibits BeWo cell fusion through activation of STAT3. Understanding the effects of free plasma heme in pregnant women either due to malaria, sickle cell disease or other hemolytic diseases, will enable identification of high-risk women and may lead to discovery of new drug targets against associated adverse pregnancy outcome.
authors: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310, United States of America.
authors: Mingli
authors: M
authors: Liu
authors: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310, United States of America.
authors: Salifu
authors: S
authors: Hassana
authors: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310, United States of America.
authors: Jonathan K
authors: JK
authors: Stiles
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001798:Blood Proteins; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D037161:Galectins; D015870:Gene Expression / Q000187:drug effects; D006418:Heme / Q000633:toxicity*; D006420:Hemeproteins / Q000494:pharmacology; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D010920:Placenta / Q000378:metabolism / Q000469:parasitology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D001798:Blood Proteins; C518353:ERVFRD-1 protein, human; D037502:Galectin 3; D037161:Galectins; D006420:Hemeproteins; C428445:LGALS3 protein, human; D011257:Pregnancy Proteins; D050796:STAT3 Transcription Factor; D005576:Colforsin; C020753:hemozoin; D006418:Heme; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3