{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T10:20:20Z","timestamp":1788690020103,"version":"build-2803163510"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100002923","name":"CONICET","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["20020190100041BA"],"award-info":[{"award-number":["20020190100041BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"ANPCyT","doi-asserted-by":"publisher","award":["PICT-2019- 607"],"award-info":[{"award-number":["PICT-2019- 607"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"CONICET","doi-asserted-by":"publisher","award":["PIP 2021-2023 11220200101445CO"],"award-info":[{"award-number":["PIP 2021-2023 11220200101445CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed toward the relevance of hypoxia as modulator of trophoblast cell death. Previous reports have shown that leptin, a placental cytokine, promotes cell survival in both cell culture and placental explant models. The aim of this work is to establish the role of leptin in apoptosis under hypoxic condition in trophoblast cells. In this study, we evaluated the effect of cobalt chloride, a hypoxia mimicking agent that stabilizes the expression of hypoxia-inducible factor-1 alpha, on Swan-71 and human placental explants. Hypoxia chamber was also used to generate 2% oxygen. Apoptosis was determined by the presence of apoptotic nucleus, fragmentation of DNA and Caspase-3 and PARP-1 cleavage. The pro-apoptotic proteins BAX, BID, BAD, and BAK and the anti-apoptotic effectors BCL-2, B-cell lymphoma-extra-large, and myeloid cell leukemia-1 were also analyzed. We found that hypoxia-inducible factor-1 alpha stabilization increased the appearance of apoptotic nucleus, fragmentation of DNA, and Caspase-3 and PARP-1 cleavage. Hypoxia mimicking conditions enhanced the expression of pro-apoptotic effectors BAX, BID, BAD, and BAK. Hypoxia-inducible factor-1 alpha stabilization also downregulated the level of BCL-2, B-cell lymphoma-extra-large, and myeloid cell leukemia-1. All these apoptotic parameters changes were reversed with leptin treatment. Moreover, we showed that leptin action on apoptosis modulation involves PI3K and MAPK signaling pathways. Obtained data demonstrate that hypoxia-inducible factor-1 alpha stabilization induces apoptosis in human placenta and leptin counteracts this effect, reinforcing its role as a survival cytokine.<\/jats:p>","DOI":"10.1093\/biolre\/ioae095","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T18:48:22Z","timestamp":1719341302000},"page":"708-722","source":"Crossref","is-referenced-by-count":7,"title":["Placental apoptosis increased by hypoxia inducible factor-1 stabilization is counteracted by leptin"],"prefix":"10.1093","volume":"111","author":[{"given":"Nataly","family":"de Dios","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales , Buenos Aires , Argentina"},{"name":"Universidad de Buenos Aires. CONICET. Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Riedel","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales , Buenos Aires , Argentina"},{"name":"Universidad de Buenos Aires. CONICET. Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malena","family":"Schanton","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales , Buenos Aires , Argentina"},{"name":"Universidad de Buenos Aires. CONICET. Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Balestrini","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales , Buenos Aires , Argentina"},{"name":"Universidad de Buenos Aires. CONICET. Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales , Buenos Aires , Argentina"},{"name":"Universidad de Buenos Aires. CONICET. Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"P\u00e9rez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen Macarena, Facultad de Medicina, Universidad de Sevilla Departamento de Bioqu\u00edmica M\u00e9dica y Biolog\u00eda Molecular. , Sevilla , Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Etcheverry","sequence":"additional","affiliation":[{"name":"Centro de Estudios Farmacol\u00f3gicos y Bot\u00e1nicos (CEFYBO , CONICET), , Buenos Aires , Argentina"},{"name":"Universidad de Buenos Aires. Facultad de Medicina , CONICET), , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Casale","sequence":"additional","affiliation":[{"name":"Departamento Materno-Infantil, Hospital Nacional Profesor Alejandro Posadas , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Farina","sequence":"additional","affiliation":[{"name":"Centro de Estudios Farmacol\u00f3gicos y Bot\u00e1nicos (CEFYBO , CONICET), , Buenos Aires , Argentina"},{"name":"Universidad de Buenos Aires. Facultad de Medicina , CONICET), , Buenos Aires , Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"S\u00e1nchez-Margalet","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen Macarena, Facultad de Medicina, Universidad de Sevilla Departamento de Bioqu\u00edmica M\u00e9dica y Biolog\u00eda Molecular. , Sevilla , Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julieta","family":"Maym\u00f3","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales , Buenos Aires , Argentina"},{"name":"Universidad de Buenos Aires. CONICET. 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