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Induction of apoptosis increases SUMO‐1 protein expression and conjugation in mouse periovulatory granulosa cells in vitro
Author(s) -
Shao Ruijin,
Rung Emilia,
Weijdegård Birgitta,
Billig Håkan
Publication year - 2006
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.20386
Subject(s) - biology , granulosa cell , apoptosis , microbiology and biotechnology , dna fragmentation , programmed cell death , sumo protein , endocrinology , ovary , ubiquitin , genetics , gene
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. Mol. Reprod. Dev. © 2005 Wiley‐Liss, Inc.