Next Article in Journal
Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis
Next Article in Special Issue
A Co-Culture Model of Fibroblasts and Adipose Tissue-Derived Stem Cells Reveals New Insights into Impaired Wound Healing After Radiotherapy
Previous Article in Journal
Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study
Previous Article in Special Issue
Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(10), 25450-25465; doi:10.3390/ijms161025450

TP53inp1 Gene Is Implicated in Early Radiation Response in Human Fibroblast Cells

1
Division of Molecular Radiobiology, National Public Health Center—National Research Directorate for Radiobiology and Radiohygiene, Anna 5, Budapest 1221, Hungary
2
Doctoral School of Pathological Sciences, Semmelweis University, Üllői 26, Budapest 1089, Hungary
3
Department of Genetics, Cell and Immunobiology, Semmelweis University, Nagyvárad tér 4, Budapest 1089, Hungary
4
Department of Morphology and Physiology, College of Health Care, Semmelweis University, Vas 17, Budapest 1089, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 30 June 2015 / Revised: 15 September 2015 / Accepted: 20 October 2015 / Published: 23 October 2015
(This article belongs to the Collection Radiation Toxicity in Cells)
View Full-Text   |   Download PDF [2310 KB, uploaded 23 October 2015]   |  

Abstract

Tumor protein 53-induced nuclear protein-1 (TP53inp1) is expressed by activation via p53 and p73. The purpose of our study was to investigate the role of TP53inp1 in response of fibroblasts to ionizing radiation. γ-Ray radiation dose-dependently induces the expression of TP53inp1 in human immortalized fibroblast (F11hT) cells. Stable silencing of TP53inp1 was done via lentiviral transfection of shRNA in F11hT cells. After irradiation the clonogenic survival of TP53inp1 knockdown (F11hT-shTP) cells was compared to cells transfected with non-targeting (NT) shRNA. Radiation-induced senescence was measured by SA-β-Gal staining and autophagy was detected by Acridine Orange dye and microtubule-associated protein-1 light chain 3 (LC3B) immunostaining. The expression of TP53inp1, GDF-15, and CDKN1A and alterations in radiation induced mitochondrial DNA deletions were evaluated by qPCR. TP53inp1 was required for radiation (IR) induced maximal elevation of CDKN1A and GDF-15 expressions. Mitochondrial DNA deletions were increased and autophagy was deregulated following irradiation in the absence of TP53inp1. Finally, we showed that silencing of TP53inp1 enhances the radiation sensitivity of fibroblast cells. These data suggest functional roles for TP53inp1 in radiation-induced autophagy and survival. Taken together, we suppose that silencing of TP53inp1 leads radiation induced autophagy impairment and induces accumulation of damaged mitochondria in primary human fibroblasts. View Full-Text
Keywords: TP53inp1; p53-network; autophagy; senescence; radiosensitivity; RNA interference; GDF-15; CDKN1A TP53inp1; p53-network; autophagy; senescence; radiosensitivity; RNA interference; GDF-15; CDKN1A
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Sándor, N.; Schilling-Tóth, B.; Kis, E.; Fodor, L.; Mucsányi, F.; Sáfrány, G.; Hegyesi, H. TP53inp1 Gene Is Implicated in Early Radiation Response in Human Fibroblast Cells. Int. J. Mol. Sci. 2015, 16, 25450-25465.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top