RRC ID 69456
Author Uemura T, Tanaka Y, Higashi K, Miyamori D, Takasaka T, Nagano T, Toida T, Yoshimoto K, Igarashi K, Ikegaya H.
Title Acetaldehyde-induced cytotoxicity involves induction of spermine oxidase at the transcriptional level.
Journal Toxicology
Abstract Ethanol consumption causes serious liver injury including cirrhosis and hepatocellular carcinoma. Ethanol is metabolized mainly in the liver to acetic acid through acetaldehyde. We investigated the effect of ethanol and acetaldehyde on polyamine metabolism since polyamines are essential factors for normal cellular functions. We found that acetaldehyde induced spermine oxidase (SMO) at the transcriptional level in HepG2 cells. The levels and activities of ornithine decarboxylase (ODC) and spermidine/spermine acetyltransferase (SSAT) were not affected by acetaldehyde. Spermidine content was increased and spermine content was decreased by acetaldehyde treatment. Knockdown of SMO expression using siRNA reduced acetaldehyde toxicity. Acetaldehyde exposure increased free acrolein levels. An increase of acrolein by acetaldehyde was SMO dependent. Our results indicate that cytotoxicity of acetaldehyde involves, at least in part, oxidation of spermine to spermidine by SMO, which is induced by acetaldehyde.
Volume 310
Pages 1-7
Published 2013-8-9
DOI 10.1016/j.tox.2013.05.008
PII S0300-483X(13)00129-7
PMID 23707493
MeSH Acetaldehyde / toxicity* Acetyltransferases / metabolism Acrolein / metabolism Blotting, Western Cell Proliferation / drug effects Cell Survival / drug effects Enzyme Induction Ethanol / toxicity* Hep G2 Cells Humans Ornithine Decarboxylase / metabolism Oxidation-Reduction Oxidoreductases Acting on CH-NH Group Donors / biosynthesis* Oxidoreductases Acting on CH-NH Group Donors / genetics Polyamines / metabolism RNA, Small Interfering / genetics Reverse Transcriptase Polymerase Chain Reaction Transcription, Genetic*
IF 4.099
Human and Animal Cells Hep G2(RCB1886)