Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardiomyocyte-derived cell line H9c2.
We investigated cell death during glucose deprivation in rat cardiomyocyte-derived H9c2 cells. Electron microscopic analysis revealed accumulation of autophagic vacuoles during glucose deprivation. The addition of 3-methyladenine or LY294002, which are known to inhibit autophagosome formation, reduced cell death while Z-VAD-FMK, a caspase inhibitor, slightly affected cell death. Thus, cell death during glucose deprivation is not type I programmed cell death (apoptotic cell death) but type II programmed cell death (autophagic cell death). Moreover, we found that both insulin-like growth factor-I and the adenovirus-mediated overexpression of wild-type class I PI 3-kinase accelerated cell death as well as accumulation of autophagic vacuoles during glucose deprivation while dominant-negative PI 3-kinase reduced these phenomena. The results indicate that IGF-I/PI 3-kinase accelerates the accumulation of autophagic vacuoles and subsequent autophagic cell death during glucose deprivation, revealing the opposing role of IGF-I/PI 3-kinase in two distinct types of programmed cell death (apoptotic and autophagic cell death).
Aki
Toshihiko
T
Center for Gene Research, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. taki@po.cc.yamaguchi-u.ac.jp
Yamaguchi
Kazuhito
K
Fujimiya
Tatsuya
T
Mizukami
Yoichi
Y
D000818:Animals; D001343:Autophagy / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D005947:Glucose / Q000172:deficiency*; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D014617:Vacuoles / Q000378:metabolism
D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose