Affordable Access

deepdyve-link
Publisher Website

Activated p53 in the anti-apoptotic milieu of tuberous sclerosis gene mutation induced diseases leads to cell death if thioredoxin reductase is inhibited.

Authors
  • Abdelwahab, ElHusseiny M M1, 2
  • Bovari-Biri, Judit1, 2
  • Smuk, Gabor3
  • Fillinger, Janos4, 5
  • McPhail, Donald6
  • Krymskaya, Vera P7
  • Pongracz, Judit E8, 9, 10
  • 1 Department of Pharmaceutical Biotechnology, University of Pecs, Pecs, Hungary. , (Hungary)
  • 2 Szentagothai Research Centre, University of Pecs, 20 Ifjusag Str., Pecs, 7624, Hungary. , (Hungary)
  • 3 Department of Pathology, University of Pecs, Pecs, Hungary. , (Hungary)
  • 4 Department of Pathology, Semmelweis University, Budapest, Hungary. , (Hungary)
  • 5 National Koranyi Institute of Pulmonology, Budapest, Hungary. , (Hungary)
  • 6 Cell Protx Ltd, Aberdeen, UK.
  • 7 Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
  • 8 Department of Pharmaceutical Biotechnology, University of Pecs, Pecs, Hungary. [email protected] , (Hungary)
  • 9 Szentagothai Research Centre, University of Pecs, 20 Ifjusag Str., Pecs, 7624, Hungary. [email protected] , (Hungary)
  • 10 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pecs, 2 Rokus Str, Pecs, 7624, Hungary. [email protected] , (Hungary)
Type
Published Article
Journal
APOPTOSIS
Publisher
Springer-Verlag
Publication Date
Jun 01, 2021
Volume
26
Issue
5-6
Pages
253–260
Identifiers
DOI: 10.1007/s10495-021-01670-4
PMID: 33860865
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Tuberous sclerosis, angiomyolipoma and lymphangioleiomyomatosis are a group of diseases characterized by mutation in tuberous sclerosis genes (TSC 1-2). TSC mutation leads to continuous activation of the mTOR pathway that requires adaptation to increased ATP requirement. With limited treatment options, there is an increasing demand to identify novel therapeutic targets and to understand the correlations between mTOR pathway activation and the lack of cell death in the presence of TSC mutation. In the current study, we demonstrate deregulation of p53 controlled and mitochondria associated cell death processes. The study also reveals that treatment of TSC mutant cells with the drug candidate Proxison combined with reduced concentration of rapamycin can increase production of reactive oxygen species (ROS), can modify miRNA expression pattern associated with p53 regulation and can reduce cell viability.

Report this publication

Statistics

Seen <100 times