title: Fate of isolated adult cardiomyocytes undergoing starvation-induced autophagic degeneration.
abstract: We induced autophagy in isolated adult rat ventricular cardiomyocytes by incubating them in glucose-free medium supplemented with mannitol for up to 4 days. The upregulation of LC3 and vacuoles containing partially degraded subcellular organelles were readily apparent in glucose-starved cells. Most dead cells in both groups showed features of necrosis, although the survival rate was significantly lower among glucose-starved cells than among the controls. In contrast, the rate of apoptosis was about the same in both groups. Two inhibitors of autophagy, 3-methyladenine (3-MA) and leupeptin, significantly reduced the viability of both control and glucose-starved cells in a dose-dependent manner and caused specific morphological alterations: 3-MA reduced the number of autophagic vacuoles, whereas leupeptin greatly increased their number and size. Conversely, rapamycin, an enhancer of autophagy, improved the survival of glucose-starved cells. The reduction in cellular ATP caused by glucose depletion was exacerbated by the inhibitors but mitigated by rapamycin, suggesting that inhibition of autophagy may accelerate energy depletion, leading to necrosis. Our findings suggest that in cardiomyocytes, autophagy is a compensatory, prosurvival response to stress, and that autophagic death is an unsuccessful outcome brought on by necrosis.
authors.affiliation: Division of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan. gt@gifu-u.ac.jp
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Rumi
authors.initials: R
authors.lastname: Maruyama
authors.forename: Kazuko
authors.initials: K
authors.lastname: Goto
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kanamori
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsujimoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D001343:Autophagy; D002469:Cell Separation; D048430:Cell Shape; D003470:Culture Media; D005947:Glucose / Q000172:deficiency*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000648:ultrastructure; D051381:Rats
chemical_list: D003470:Culture Media; D005947:Glucose