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Increased hepatocyte organelle injury via autophagy in old rats subjected to an environmental challenge
Author(s) -
Zhang Hannah J.,
Kregel Kevin C.,
Oberley Terry D.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1451-a
Subject(s) - autophagy , hepatocyte , mitochondrion , organelle , vacuole , microbiology and biotechnology , ultrastructure , peroxisome , lipid droplet , biology , liver injury , chemistry , apoptosis , cytoplasm , biochemistry , endocrinology , anatomy , in vitro , gene
We previously demonstrated that environmental challenge produces exaggerated liver injury with aging. The current study evaluated potential mechanisms contributing to age‐related subcellular ultrastructural changes in the liver following a heat stress protocol. Young and old rats were heat‐stressed on consecutive days. Liver samples were harvested over a 48‐h period after the second heating and processed for electron microscopy (EM). Ultrastructural morphometric analysis of injury in selected cellular organelles and compartments was performed. Heat stress produced substantial mitochondrial damage in hepatocytes up to 48 h post‐heating in both age groups, with significantl higher damage ratios in old livers between 0.5 and 6 h. Old livers also had striking increases in autophagy, which peaked at 1 h post‐heating. Both mitochondria and peroxisomes were present in the autophagic vacuoles. Significant apoptosis was not observed at the EM level in either age group. The presence of myelin figures, which reflects lipid injury, increased with heating and was more prevalent in old livers. These data demonstrate that mitochondria and peroxisomes in old hepatocytes are very susceptible to heat stress‐induced injury in vivo, which may be a primary factor contributing to the decline in stress tolerance with aging. These findings also suggest that an autophagic death pathway involving both mitochondria and peroxisomes may play an important role in heat‐induced hepatocyte injury in old organisms. Supported by NIH AG12350.