title: Effect of selected NAD+ analogues on mitochondria activity and proliferation of endothelial EA.hy926 cells.
abstract: The aim of the study was to examine the effect of 1-methylnicotinamide (MNA) and 1-methyl-3-nitropyridine (MNP) on mitochondria activity and proliferation of endothelial EA.hy926 cells. The activity of MNA was also referred to nicotinamide (NAM) being MNA metabolic precursor. NAM and MNA used at high concentrations (up to 1 mM) had no effect on mitochondria metabolism and proliferation of EA.hy926 cells. It could be related to the fact that these compounds hardly cross the cell membrane. It supports the results of our previous study suggesting that anti-inflammatory and anti-thrombotic effects of MNA could be associated with its ability to bind to glycosaminoglycans, especially heparins, located on the endothelium membrane without entering into target cells. In contrast, MNP caused substantial changes in mitochondria activity and proliferation of EA.hy926 cells. This compound used at low concentrations (below 100 microM) blocked the cell cycle of EA.hy926 cells in G1 phase and was very effective in inhibiting cell growth (IC50=13.8+/-2.4 microM). At higher concentrations (0.1-1 mM) MNP caused a significant reduction of cell survival. The observed effects of MNP could be related, at least in part, to its ability to influence the ATP and NAD+ intracellular levels. MNP caused also important changes in Ca2+ intracellular concentration, significant decrease in inner mitochondrial membrane potential and high increase in mitochondrial respiration of EA.hy926 cells. The observed effects of MNP may be related in part to its cellular metabolites detected after 45 min incubation with 250 microM MNP.
authors.affiliation: Department of Biochemistry, University of Szczecin, 3c Felczaka St, 71-412 Szczecin, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Nowak
authors.forename: Antoni
authors.initials: A
authors.lastname: Wrzosek
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Łukasiak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rutkowska
authors.forename: Jan
authors.initials: J
authors.lastname: Adamus
authors.forename: Jerzy
authors.initials: J
authors.lastname: Gebicki
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Dołowy
authors.forename: Adam
authors.initials: A
authors.lastname: Szewczyk
authors.forename: Jolanta
authors.initials: J
authors.lastname: Tarasiuk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009243:NAD / Q000031:analogs & derivatives* / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C488480:1-methyl-3-nitropyridinium; D011725:Pyridines; D011726:Pyridinium Compounds; D009243:NAD; D009536:Niacinamide; D000255:Adenosine Triphosphate; D010100:Oxygen; D002118:Calcium; C024058:N(1)-methylnicotinamide