title: Functional significance and morphological characterization of starvation-induced autophagy in the adult heart.
abstract: To examine the functional significance and morphological characteristics of starvation-induced autophagy in the adult heart, we made green fluorescent protein-microtubule-associated protein 1-light chain 3 (LC3) transgenic mice starve for up to 3 days. Electron microscopy revealed round, homogenous, electron-dense lipid droplet-like vacuoles that initially appeared in cardiomyocytes as early as 12 hours after starvation; these vacuoles were identified as lysosomes based on cathepsin D-immunopositive reactivity and acid phosphatase activity. The increase in the number of lysosomes depended on the starvation interval; typical autophagolysosomes with intracellular organelles also appeared, and their numbers increased at the later phases of starvation. Myocardial expression of autophagy-related proteins, LC3-II, cathepsin D, and ubiquitin, increased, whereas both myocardial ATP content and starvation integral decreased. Treatment with bafilomycin A1, an autophagy inhibitor, did not affect cardiac function in normally fed mice but significantly depressed cardiac function and caused significant left ventricular dilatation in mice starved for 3 days. The cardiomyocytes were occupied with markedly accumulated lysosomes in starved mice treated with bafilomycin A1, and both the myocardial amino acid content, which was increased during starvation, and the myocardial ATP content were severely decreased, potentially contributing to cardiac dysfunction. The present findings suggest a critical role of autophagy in the maintenance of cardiac function during starvation in the adult.
authors.affiliation: Department of Laboratory Medicine, Division of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kanamori
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: Akiko
authors.initials: A
authors.lastname: Tsujimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogino
authors.forename: Longhu
authors.initials: L
authors.lastname: Li
authors.forename: Itta
authors.initials: I
authors.lastname: Kawamura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takeyama
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Kenshi
authors.initials: K
authors.lastname: Nagashima
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi