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Induction of apoptosis increases SUMO-1 protein expression and conjugation in mouse periovulatory granulosa cells in vitro

Journal article
Authors Linus Ruijin Shao
Emilia Rung
Birgitta Weijdegård
Håkan Billig
Published in Molecular reproduction and development
Volume 73
Issue 1
Pages 50-60
ISSN 1040-452X (Print)
Publication year 2006
Published at Institute of Neuroscience and Physiology, Department of Physiology
Pages 50-60
Language en
Links dx.doi.org/10.1002/mrd.20386
Keywords Animals, Apoptosis/*physiology, Caspase 3, Caspases/metabolism, Cell Nucleus/metabolism, Cells, Cultured, Ceramides/physiology, Female, Granulosa Cells/*metabolism, Mice, Mice, Inbred C57BL, Receptors, Progesterone/metabolism, SUMO-1 Protein/biosynthesis/*genetics
Subject categories Medical and Health Sciences, Physiology

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.

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