Mouse mammary gland involution is associated with cytochrome c release and caspase activation |
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Authors: | Marti A Ritter P M Jäger R Lazar H Baltzer A Schenkel J Declercq W Vandenabeele P Jaggi R |
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Institution: | Department of Clinical Research, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland. andreas.marti@dfk4.unibe.ch |
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Abstract: | At weaning, milk producing mammary epithelial cells undergo apoptosis and are removed by phagocytosis. Here, we show that mouse mammary gland involution is associated with mitochondrial cytochrome c release and processing of numerous caspases, including caspase-1, -3, -7, -8 and -9. Induction of caspase-3-like activity paralleled cleavage of poly-(ADP--ribose) polymerase. Dexamethasone inhibited processing of caspase-3, -7 and -8 and apoptosis, but had no effect on caspase-1 accumulation and cytochrome c release. In Bcl-2 transgenic animals, cytochrome c release, caspase activation and apoptosis were impaired. Thus, the pro-apoptotic signaling pathway in mammary epithelial cells during involution involves the release of cytochrome c and activation of caspases. It is inhibited by Bcl-2 at the mitochondrial level and by dexamethasone at a post-mitochondrial level. |
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