title: Kynuramines induce overexpression of heat shock proteins in pancreatic cancer cells via 5-hydroxytryptamine and MT1/MT2 receptors.
abstract: Kynuramines, metabolites of melatonin and L-tryptophan, are synthesized endogenously by oxygenases or in spontaneous reaction by an interaction with free radicals. We have reported previously that melatonin stimulates expression and phosphorylation of heat shock protein (HSP) 27, as well as production of HSP70 and HSP90αβ in pancreatic carcinoma cells (PANC-1). Based on those results, we hypothesized that above processes could have been involved in the interruption of intrinsic proapoptotic pathway. Herein, we report that incubation of PANC-1 cells with N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) or with L-kynurenine (L-KYN) lead to the overexpression of heat shock protein synthesis and these effects are partially reversed by 5-HT3 or MT1/MT2 receptor antagonists. PANC-1 cells in culture were treated with AFMK or L-KYN, with non selective MT1/MT2 receptor antagonist (luzindole), with 5-HT2 and 5-HT3 receptor antagonists (ketanserin and MDL72222), or combination of these substances. Both AFMK and L-KYN significantly decreased cytoplasmic HSP27 and this effect was presumably due to increased of its phosphorylation and consequent nuclear translocation, confirmed by immunoprecipitation of phosphorylated form of HSP27. These changes were accompanied by marked augmentation of HSP70 and HSP90αβ in the cytosolic fraction. Pretreatment of cell cultures with luzindole or MDL72222 followed by the addition of AFMK or L-KYN reversed the stimulatory effects of these substances on HSP expression in PANC-1 cells, whereas ketanserin failed to influence mentioned above phenomenon. We conclude that activation of HSPs in pancreatic carcinoma cells seems to be dependent on an interaction of AFMK or L-KYN with MT1/MT2 or/and 5-HT3 receptors.
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Cracow, Poland. a.leja-szpak@uj.edu.pl.
authors.forename: A
authors.initials: A
authors.lastname: Leja-Szpak
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Pierzchalski
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Goralska
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Nawrot-Porabka
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Bonior
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Link-Lenczowski
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Jastrzebska
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Jaworek
mesh_terms: D045744:Cell Line, Tumor; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D007735:Kynuramine / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014326:Tropanes / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D014326:Tropanes; D014363:Tryptamines; C057154:luzindole; D012701:Serotonin; D007735:Kynuramine; D014364:Tryptophan; D007650:Ketanserin; D008550:Melatonin; C042253:bemesetron