title: Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows.
abstract: Programmed necrosis (necroptosis) is an alternative form of programmed cell death that is regulated by receptor-interacting protein kinase (RIPK) 1 and 3-dependent, but is a caspase (CASP)-independent pathway. In the present study, to determine if necroptosis participates in bovine structural luteolysis, we investigated RIPK1 and RIPK3 expression throughout the estrous cycle, during prostaglandin F2α (PGF)-induced luteolysis in the bovine corpus luteum (CL), and in cultured luteal steroidogenic cells (LSCs) after treatment with selected luteolytic factors. In addition, effects of a RIPK1 inhibitor (necrostatin-1, Nec-1; 50 μM) on cell viability, progesterone secretion, apoptosis related factors and RIPKs expression, were evaluated. Expression of RIPK1 and RIPK3 increased in the CL tissue during both spontaneous and PGF-induced luteolysis (P < 0.05). In cultured LSCs, tumor necrosis factor α (TNF; 2.3 nM) in combination with interferon γ (IFNG; 2.5 nM) up-regulated RIPK1 mRNA and protein expression (P < 0.05). TNF + IFNG also up-regulated RIPK3 mRNA expression (P < 0.05), but not RIPK3 protein. Although Nec-1 prevented TNF + IFNG-induced cell death (P < 0.05), it did not affect CASP3 and CASP8 expression. Nec-1 decreased both RIPK1 and RIPK3 protein expression (P < 0.05). These findings suggest that RIPKs-dependent necroptosis is a potent mechanism responsible for bovine structural luteolysis induced by pro-inflammatory cytokines.
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, 10-748, Poland.
authors.forename: Takuo
authors.initials: T
authors.lastname: Hojo
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, 10-748, Poland.
authors.forename: Marta J
authors.initials: MJ
authors.lastname: Siemieniuch
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, 10-748, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Lukasik
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, 10-748, Poland.
authors.forename: Katarzyna K
authors.initials: KK
authors.lastname: Piotrowska-Tomala
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, 10-748, Poland.
authors.forename: Agnieszka W
authors.initials: AW
authors.lastname: Jonczyk
authors.affiliation: Graduate School of Environmental and Life Science, Okayama University, Okayama, 700-8530, Japan.|Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, 080-8555, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okuda
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, 10-748, Poland.
authors.forename: Dariusz J
authors.initials: DJ
authors.lastname: Skarzynski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D030762:Estrous Cycle / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D008184:Luteal Cells / Q000166:cytology / Q000378:metabolism*; D003341:Luteolysis / Q000187:drug effects; D009336:Necrosis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015237:Dinoprost; D053422:Receptor-Interacting Protein Serine-Threonine Kinases