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The Role of Apoptosis in Acetaminophen‐Induced Injury
Author(s) -
KASS GEORGE E. N.,
MACANASPIRARD PATRICIA,
LEE PAULINE C.,
HINTON RICHARD H.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.103
Subject(s) - apoptosis , hepatoblastoma , cytochrome c , caspase , intrinsic apoptosis , acetaminophen , microbiology and biotechnology , chemistry , mitochondrion , cleavage (geology) , caspase 3 , cytosol , programmed cell death , biology , biochemistry , medicine , enzyme , paleontology , fracture (geology)
A bstract : Apoptosis plays a critical role in acetaminophen (AAP)‐induced hepatic injury, since inhibiting apoptosis also prevents the development of acute liver failure. In this study, the mechanism of apoptosis induction by AAP was investigated in the human hepatoblastoma cell line HuH7. AAP caused marked cytotoxicity in HuH7 cells as a result of apoptosis. Processing of execution caspases to their corresponding active fragments and cleavage of cytokeratin‐18 were observed, supporting a role of caspases in AAP‐induced apoptosis. The manifestation of apoptosis was preceded by a translocation of cytochrome c from mitochondria to the cytosol. In conclusion, AAP induces apoptosis in human hepatoblastoma HuH7 cells through mitochondrial cytochrome c release and caspase activation.