ABSTRACT
Depletion of intracellular zinc by N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces p53-mediated protein synthesis-dependent apoptosis of mouse cortical neurons. Here, we examined the requirement for poly(ADP-ribose) polymerase (PARP)-1 as an upstream regulator of p53 in zinc depletion-induced neuronal apoptosis. First, we found that chemical inhibition or genetic deletion of PARP-1 markedly attenuated TPEN-induced apoptosis of cultured mouse cortical neurons. Poly(ADP-ribosyl)ation of p53 occurred starting 1 h after TPEN treatment. Suggesting the critical role of PARP-1, the TPEN-induced increase of stability and activity of p53 as well as poly(ADP-ribosyl)ation of p53 was almost completely blocked by PARP inhibition. Consistent with this, the induction of downstream proapoptotic proteins PUMA and NOXA was noticeably reduced by chemical inhibitors or genetic deletion of PARP-1. TPEN-induced cytochrome C release into the cytosol and caspase-3 activation were also blocked by inhibition of PARP-1. Taken together, these findings indicate that PARP-1 is essential for TPEN-induced neuronal apoptosis.
Subject(s)
Apoptosis/physiology , Ethylenediamines/pharmacology , Neurons/cytology , Neurons/drug effects , Poly(ADP-ribose) Polymerases/metabolism , Tumor Suppressor Protein p53/metabolism , Zinc/metabolism , Animals , Apoptosis/drug effects , Immunohistochemistry , Mice , Microscopy, Confocal , Neurons/metabolism , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Protein Processing, Post-Translational , Zinc/deficiencyABSTRACT
Peripherally inserted central catheters (PICCs) are expected to be convenient and reliable venous access devices. The purpose of this study was to analyze clinical nurse specialist (CNS)-led PICC placement and to describe its growth in a tertiary hospital. A computerized database identified 3508 patients who had PICCs placed between November 2001 and June 2010. One thousand, eight hundred ninety-eight of the 4101 PICCs were available for complete follow-up, and 791 of 1898 PICCs were still in place. The mean dwell time of 1898 PICCs was 27.4 days (1â¼422 days). Most PICCs were removed after the completion of infusion therapy; the remainder were removed following death, occlusion, suspected infection, or phlebitis, or were removed by the patient. The study found that CNS-led PICC placement for infusion therapies was effective and safe with relatively low complication rates and that CNSs played important roles in the increased use of PICCs.
Subject(s)
Catheterization, Peripheral/methods , Specialties, Nursing/organization & administration , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Republic of Korea , Retrospective Studies , Young AdultABSTRACT
Depletion of intracellular zinc with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induces protein synthesis-dependent apoptosis. In this study, we examined the requirement for p53 as an upstream transcription factor in TPEN-induced neuronal apoptosis. Chemical or genetic blockade of p53 markedly attenuated TPEN-induced neuronal apoptosis, while the stability and activity of p53 were increased by TPEN. In addition, expression of proapoptotic genes, PUMA and NOXA, and activation of caspase-11 were increased by TPEN in a p53-dependent manner. Inhibition of p53 blocked cytochrome C release from mitochondria to cytosol and prevented caspase-3 activation. Therefore, p53 may be an essential regulatory factor for TPEN-induced neuronal apoptosis.
