title: Heat shock stimulates polyamine oxidation by two distinct mechanisms in mammalian cell cultures.
abstract: Heat shock stimulates both exogenous and endogenous polyamine oxidation in mammalian cells, but by distinct biochemical mechanisms. Exogenously added polyamines are oxidized in serum via the temperature-dependent activation of a single class of enzymes, the copper-dependent amine oxidases. Endogenous polyamines undergo a two-step reaction sequence involving acetylation by a heat-inducible acetyltransferase and subsequent oxidation by a constitutively expressed, flavin-dependent polyamine oxidase. In both instances, polyamine oxidation generates hydrogen peroxide and reactive aldehydes which influence cell viability as demonstrated by inhibitor studies. Aminoguanidine, an inhibitor of the copper-dependent amine oxidases, confers protection to cells during either a severe 43 degrees C heat shock or a relatively nontoxic heat stress followed by incubation at 37 degrees C, all in the presence of exogenous spermidine. Specific inhibition of the endogenous polyamine oxidase will also confer partial survival protection after heat shock, but only in cultures that have been previously depleted of cellular glutathione. These data confirm that hyperthermic stress can generate an oxidative stress in mammalian cells via induction of polyamine oxidation. Further, through distinct extracellular and intracellular mechanisms, these temperature-dependent polyamine oxidation reactions can modulate cell viability.
authors.affiliation: University of Arizona Health Sciences Center, Department of Radiation Oncology, Tucson 85724.
authors.forename: P M
authors.initials: PM
authors.lastname: Harari
authors.forename: D J
authors.initials: DJ
authors.lastname: Fuller
authors.forename: E W
authors.initials: EW
authors.lastname: Gerner
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D006358:Hot Temperature; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D011073:Polyamines / Q000008:administration & dosage / Q000378:metabolism*; D013312:Stress, Physiological / Q000201:enzymology; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase