RRC ID 6031
Author Kanamori H, Takemura G, Maruyama R, Goto K, Tsujimoto A, Ogino A, Li L, Kawamura I, Takeyama T, Kawaguchi T, Nagashima K, Fujiwara T, Fujiwara H, Seishima M, Minatoguchi S.
Title Functional significance and morphological characterization of starvation-induced autophagy in the adult heart.
Journal Am. J. Pathol.
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.
Volume 174(5)
Pages 1705-14
Published 2009-5
DOI 10.2353/ajpath.2009.080875
PII S0002-9440(10)61028-0
PMID 19342365
PMC PMC2671259
MeSH Adenosine Triphosphate / metabolism Animals Apoptosis / drug effects Apoptosis / physiology Autophagy* Body Weight / drug effects Cathepsin D / metabolism Enzyme Inhibitors / pharmacology Fluorescent Antibody Technique Green Fluorescent Proteins / genetics Heart Function Tests Immunoenzyme Techniques Lysosomes / metabolism Lysosomes / ultrastructure Macrolides / pharmacology Mice Mice, Transgenic Microtubule-Associated Proteins / physiology* Myocytes, Cardiac / cytology* Myocytes, Cardiac / metabolism Myocytes, Cardiac / ultrastructure* Proton-Translocating ATPases / antagonists & inhibitors Rats Ubiquitin / metabolism Vacuoles / metabolism Vacuoles / ultrastructure Ventricular Dysfunction, Left / metabolism
IF 4.069
Times Cited 75
Mice GFP-LC3#53