title: Roles of inhibitors of poly(ADP-ribose) polymerase in protecting rat RINm5F cell line against free fatty acid-induced apoptosis.
abstract: BACKGROUND
  Chronic exposure to high levels of free fatty acid (FFA) has adverse effects on the function of pancreatic beta-cell, with a consequent increase in the production of reactive oxygen species. Poly (ADP-Ribose) polymerase (PARP-1) overactivation leads to massive NAD(+) consumption and ATP depletion with induction of cellular necrosis under high reactive oxygen species. In the present study, we investigated whether inhibitors of poly(ADP-ribose) polymerase were capable of protecting beta-cells from death induced by extended exposure to FFA.
  
  
  METHODS
  RINm5F cell line was cultured in the presence of FFA (palmitate) in order to induce apoptosis, and then cells were treated with low-potency poly(ADP-ribose) polymerase inhibitor (3-aminobenzamide) or potent poly(ADP-ribose) polymerase inhibitor (PJ34). In order to explore whether poly(ADP-ribose) polymerase inhibitors could inhibit the apoptosis induced by FFA, expression of PARP-1 was measured by RT-qPCR and Western blot, while the apoptosis of RINm5F cells were analyzed by flow cytometry and Tdt-mediated dUTP Nick-End Labeling(TUNEL).
  
  
  RESULTS
  Low-potency poly(ADP-ribose) polymerase inhibitor (3-aminobenzamide) significantly suppressed the impaired insulin secretion and FFA-induced apoptosis (P<0.01). However, potent poly(ADP-ribose) polymerase inhibitor (PJ34) had no significant effects on FFA-induced apoptosis (P>0.05). Moreover, low-potency inhibitors of PARP-1 increased PDX-1 expression down-regulated by FFA-treatment.
  
  
  CONCLUSIONS
  These findings suggested that low-potency inhibitors of poly(ADP-ribose) polymerases could protect rat RINm5F cell line against free fatty acid-induced apoptosis, and it was through regulatory pathway of regulating PDX-1 expression.
authors.affiliation: Department of Endocrinology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Mao
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Pan
authors.forename: B
authors.initials: B
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: Q
authors.initials: Q
authors.lastname: Zeng
authors.forename: X
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000201:enzymology*; D010616:Phenanthrenes / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis*; D051381:Rats; D015534:Trans-Activators / Q000096:biosynthesis
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D018398:Homeodomain Proteins; D007328:Insulin; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C025160:3-aminobenzamide; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases