title: Acetaldehyde-induced cytotoxicity involves induction of spermine oxidase at the transcriptional level.
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.
authors.affiliation: Department of Forensic Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Sciences, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. tuemura@koto.kpu-m.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uemura
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kyohei
authors.initials: K
authors.lastname: Higashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miyamori
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Takasaka
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nagano
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegaya
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity*; D000123:Acetyltransferases / Q000378:metabolism; D000171:Acrolein / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004790:Enzyme Induction; D000431:Ethanol / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000096:biosynthesis* / Q000235:genetics; D011073:Polyamines / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
chemical_list: D000079:Acetaldehyde; D000123:Acetyltransferases; D000171:Acrolein; D000431:Ethanol; D009955:Ornithine Decarboxylase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D034741:RNA, Small Interfering; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
keywords: Acetaldehyde; Acrolein; CH(3)CHO; Cr-PdG; EtOH; GAPDH; ODC; Polyamine; SMO; SSAT; Spermine oxidase; acetaldehyde; ethanol; glyceraldehyde 3-phosphate dehydrogenase; ornithine decarboxylase; spermidine spermine acetyltransferase; spermine oxidase; α-methyl-γ-hydroxy-1,N(2)-propano-2′-deoxyguanosine