Mouse mammary gland involution is associated with cytochrome c release and caspase activation.
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.
Marti
A
A
Department of Clinical Research, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland. andreas.marti@dfk4.unibe.ch
Ritter
P M
PM
Jäger
R
R
Lazar
H
H
Baltzer
A
A
Schenkel
J
J
Declercq
W
W
Vandenabeele
P
P
Jaggi
R
R
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
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