The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death

Abstract

Abstract. Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor (AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG), the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2 and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.

Poly(ADP-ribose) polymerase-1 in high glucose-induced epithelial-mesenchymal transition during peritoneal fibrosis

“…Suckau et al (24) reported on targeted RNAi for the treatment of heart failure. Cohausz et al (25) found that PARP-1 siRNA could down-regulated PARP-1 protein expression, it was confirmed by immunofluorescence. Our data indicate that high glucose up-regulated PARP-1 mRNA and protein expression in HPMCs, and PARP-1 siRNA may partly inhibit PARP-1 expession.…”

Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase

“…To conduct a direct assessment of the potential relationship between PARP and minocycline in a lung injury setting, we examined whether treatment with minocycline blocked PARP activation mediated by the potent DNA alkylating agent MNNG (27,28). Mice, pretreated with the same dose of minocycline used to achieve the anti-inflammatory effects described above, received an intratracheal administration of 10 mg/kg MNNG and were sacrificed 1 h later.…”

Cell Death and Autophagy under Oxidative Stress: Roles of Poly(ADP-Ribose) Polymerases and Ca2+

“…Small interfering RNAs (siRNAs) against Becn1 (siRNA-B1; 5=-AAAGCUA CCAUUGCAUGGUCA-3= [antisense sequence]), Parp1 (siRNA-P1; 5=-AAGAGCGATGCCTATTACTGC-3= [antisense]) (7), Parp2 (siRNA-P2; 5=-AAGATGATGCCAGAGGAACTC-3= [antisense]) (7), and Trpm2 (siRNA-T2; 5=-UACUCGACCACGUAGACUCCA-3= [antisense]) (3) were obtained from Applied Biosystems. For maximal silencing efficacy, we performed silencing of Becn1 for 24 h and that of all others for 72 h. H 2 O 2 treatment.…”