title: Induction of apoptosis increases SUMO-1 protein expression and conjugation in mouse periovulatory granulosa cells in vitro.
abstract: The small ubiquitin-related modifier-1 (SUMO-1) with broad cellular expression has been implicated in a range of cellular processes, such as cell proliferation, differentiation, and apoptosis. As shown recently, SUMO-1 is expressed and regulated by gonadotropins, in particular an ovulatory hCG stimulus in mouse granulosa cells in vivo. To test the hypothesis that modulation of granulosa cell apoptosis changes SUMO-1 expression during granulosa cell differentiation in the mouse ovary, we demonstrate that progesterone receptor (PR) proteins are absent in pre-ovulatory granulosa cell nuclei, whereas they are expressed in periovulatory granulosa cell nuclei in parallel with decreases in SUMO-1 expression, caspase-3 activation, and DNA fragmentation in vivo. Second, treatment with either PR antagonists or a cell permeable ceramide analog consistently increases SUMO-1 expression in parallel with an increase in apoptosis as well as a decrease in cell proliferation in periovulatory granulosa cells in vitro. However, we do not observe an increase in SUMO-1 expression in pre-ovulatory granulosa cells that have undergone the same treatment. Third, we have also demonstrated, in pre-ovulatory granulosa cells in vitro, neither induction of spontaneous apoptosis nor the protective effect of EGF against spontaneous apoptosis changes SUMO-1 protein expression. Fourth, we show that induction of apoptosis enhances SUMO-1 conjugation in periovulatory granulosa cells in vitro, pointing to the pivotal link between the SUMO-1 conjugation and cell death. Taken together, our observations suggest that SUMO-1 via sumoylation has an important role in the regulation of granulosa cell apoptosis during granulosa cell differentiation in the mouse ovary.
authors.affiliation: Department of Physiology, Section of Endocrinology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. ruijin.shao@fysiologi.gu.se
authors.forename: Ruijin
authors.initials: R
authors.lastname: Shao
authors.forename: Emilia
authors.initials: E
authors.lastname: Rung
authors.forename: Birgitta
authors.initials: B
authors.lastname: Weijdegård
authors.forename: Håkan
authors.initials: H
authors.lastname: Billig
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002518:Ceramides / Q000502:physiology; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011980:Receptors, Progesterone / Q000378:metabolism; D025842:SUMO-1 Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D002518:Ceramides; D011980:Receptors, Progesterone; D025842:SUMO-1 Protein; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases