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Exp Clin Endocrinol Diabetes 2009; 117(6): 274-282
DOI: 10.1055/s-0029-1202794
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Roles of Inhibitors of Poly(ADP-ribose) Polymerase in Protecting Rat RINm5F Cell Line against Free Fatty Acid-induced Apoptosis

X. Mao 1 [*] , S. Wang 2 [*] , Y. Pan 2 , B. He 2 , J. Chen 2 , H. Jiang 2 , Q. Zeng 2 , X. Xu 1
  • 1Department of Endocrinology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China
  • 2Central Laboratory, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China
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Publication History

received 11.05.2008 first decision 10.06.2008

accepted 05.09.2008

Publication Date:
09 June 2009 (online)

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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.

Materials and 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.

Key words

type 2 diabetes - FFA - inhibitors of poly(ADP-ribose) polymerase - RINm5F cell line

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1 Joint first author.

Correspondence

S. WangMD, PhD 

Nanjing First Hospital Affiliated to Nanjing Medical University

210006 Nanjing

China

Phone: +86/25/8306 72 38

Fax: +86/25/5221 47 54

Email: wsk_zzy@hotmail.com