title: Chemically induced oxidative stress increases polyamine levels by activating the transcription of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase in human hepatoma HUH7 cells.
abstract: Biogenic polyamines spermine and spermidine participate in numerous cellular processes including transcription, RNA processing and translation. Specifically, they counteract oxidative stress, an alteration of cell redox balance involved in generation and progression of various pathological states including cancer. Here, we investigated how chemically induced oxidative stress affects polyamine metabolism, specifically the expression and activities of enzymes catalyzing polyamine synthesis (ornithine decarboxylase; ODC) and degradation (spermidine/spermine-N(1)-acetyltransferase; SSAT), in human hepatoma cells. Oxidative stress induced the up-regulation of ODC and SSAT gene transcription mediated by Nrf2, and in case of SSAT, also by NF-κB transcription factors. Activation of transcription led to the elevated intracellular activities of both enzymes. The balance in antagonistic activities of ODC and SSAT in the stressed hepatoma cells was shifted towards polyamine biosynthesis, which resulted in increased intracellular levels of putrescine, spermidine, and spermine. Accumulation of putrescine is indicating for accelerated degradation of polyamines by SSAT - acetylpolyamine oxidase (APAO) pathway generating toxic products that promote carcinogenesis, whereas accelerated polyamine synthesis via activation of ODC is favorable for proliferation of cells including those sub-lethally damaged by oxidative stress.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Smirnova
authors.forename: Maria G
authors.initials: MG
authors.lastname: Isaguliants
authors.forename: Mervi T
authors.initials: MT
authors.lastname: Hyvonen
authors.forename: Tuomo A
authors.initials: TA
authors.lastname: Keinanen
authors.forename: Vera L
authors.initials: VL
authors.lastname: Tunitskaya
authors.forename: Jouko
authors.initials: J
authors.lastname: Vepsalainen
authors.forename: Leena
authors.initials: L
authors.lastname: Alhonen
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Kochetkov
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ivanov
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009955:Ornithine Decarboxylase / Q000235:genetics*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics*; D011073:Polyamines / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D011073:Polyamines; D000123:Acetyltransferases; C028112:spermidine acetylase; D009955:Ornithine Decarboxylase