Role of phosphoinositide 3-kinase in the autophagic death of serum-deprived PC12 cells.
The death of serum-deprived undifferentiated PC12 cells shows both autophagic and apoptotic features. Since it is still controversial whether the autophagy is instrumental in the cell death or a mere epiphenomenon, we tested the effects of inhibiting the autophagy by a variety of phosphoinositide 3-kinase inhibitors, and provided evidence that the autophagy, or a related trafficking event, is indeed instrumental in the cell death. Furthermore, by comparing the effects of PI3-K inhibition and caspase-inhibition on autophagic and apoptotic cellular events, we showed that in this case the autophagic and apoptotic mechanisms mediate cell death by parallel pathways and do not act in series.
Guillon-Munos
A
A
Département de Biologie Cellulaire et de Morphologie, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
van Bemmelen
M X P
MX
Clarke
P G H
PG
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D002867:Chromones / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D007150:Immunohistochemistry; D008247:Lysosomes / Q000502:physiology; D008854:Microscopy, Electron; D009025:Morpholines / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats
D000135:Acid Phosphatase; D061945:Caspase Inhibitors; D002867:Chromones; D016895:Culture Media, Serum-Free; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one