title: Mouse mammary gland involution is associated with cytochrome c release and caspase activation.
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.
authors.affiliation: Department of Clinical Research, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland. andreas.marti@dfk4.unibe.ch
authors.forename: A
authors.initials: A
authors.lastname: Marti
authors.forename: P M
authors.initials: PM
authors.lastname: Ritter
authors.forename: R
authors.initials: R
authors.lastname: Jäger
authors.forename: H
authors.initials: H
authors.lastname: Lazar
authors.forename: A
authors.initials: A
authors.lastname: Baltzer
authors.forename: J
authors.initials: J
authors.lastname: Schenkel
authors.forename: W
authors.initials: W
authors.lastname: Declercq
authors.forename: P
authors.initials: P
authors.lastname: Vandenabeele
authors.forename: R
authors.initials: R
authors.lastname: Jaggi
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation; D005938:Glucocorticoids / Q000494:pharmacology; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010587:Phagocytosis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014886:Weaning
chemical_list: D003574:Cytochrome c Group; D005938:Glucocorticoids; D019253:Proto-Oncogene Proteins c-bcl-2; D003907:Dexamethasone; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; C505524:Casp7 protein, mouse; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1