title: Transport of platinum bonded nucleotides into proteoliposomes, mediated by Drosophila melanogaster thiamine pyrophosphate carrier protein (DmTpc1).
abstract: The results of the present study suggest that DmTpc1 is actively implicated in the specific uptake of free cytoplasmic Pt bonded nucleotides, and therefore could be linked to the mechanism of action of some platinum-based antitumor drugs. Although DmTpc1 has a low affinity for model [Pt(dien)(N7-5'-dGTP)] and cis-[Pt(NH3)2(py)(N7-5'-dGTP)] compared to dATP it's well known that DNA platination level of few metal atoms per double-stranded molecule may account for the pharmacological activity of platinum based antitumor drugs. This is the first investigation where it has been demonstrated that a mitochondrial carrier is directly involved in the transport of metalated purines related with the cisplatin mechanism of action. Moreover it is shown as a lower hindrance of nucleotide bonded platinum complexes could strongly enhance mitochondrial uptake. Furthermore, a new application of ICP-AES addressed to measure the transport of metalated nucleobases, by using a recombinant protein reconstituted into liposomes, has been here, for the first time, developed and compared with a standard technique such as the liquid scintillation counting.
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; IFOM Foundation, FIRC Institute of Molecular Oncology Foundation, IFOM-IEO Campus, 20139 Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Carrisi
authors.forename: Daniela
authors.initials: D
authors.lastname: Antonucci
authors.forename: Paola
authors.initials: P
authors.lastname: Lunetti
authors.forename: Danilo
authors.initials: D
authors.lastname: Migoni
authors.forename: Chiara R
authors.initials: CR
authors.lastname: Girelli
authors.forename: Vincenza
authors.initials: V
authors.lastname: Dolce
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Fanizzi
authors.forename: Michele
authors.initials: M
authors.lastname: Benedetti
authors.forename: Loredana
authors.initials: L
authors.lastname: Capobianco
mesh_terms: D001692:Biological Transport; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009711:Nucleotides / Q000737:chemistry / Q000493:pharmacokinetics; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D010984:Platinum / Q000737:chemistry* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D008081:Liposomes; D026901:Membrane Transport Proteins; D009711:Nucleotides; D009944:Organoplatinum Compounds; D011994:Recombinant Proteins; D010984:Platinum; D013835:Thiamine Pyrophosphate
keywords: Cisplatin; Drosophila melanogaster; Metalated purines; Pyriplatin; Thiamine pyrophosphate carrier