Reticulon-1C acts as a molecular switch between endoplasmic reticulum stress and genotoxic cell death pathway in human neuroblastoma cells

Federica D. Sano, Barbara Fazi, Roberta Tufi, Roberta Nardacci, Mauro Piacentini

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Damage or stress in many organelles may trigger apoptosis by several not yet fully elucidated mechanisms. A cell death pathway is induced by endoplasmic reticulum (ER) stress elicited by the unfolded protein response and/or by aberrant Ca2+ signalling. Reticulon-1C (RTN-1C) belongs to the reticulon family, neuroendocrine-specific proteins localized primarily on the ER membrane. In the present study, we demonstrate that RTN-1C is able to modulate, in a mutually exclusive way, the cellular sensitivity to different apoptosis pathways in human neuroblastoma cells. In fact, the increase of RTN-1C protein levels per se results in ER stress-induced cell death, mediated by an increase of cytosolic Ca2+, and significantly sensitizes cells to different ER stress inducers. In line with these findings, the reduction of RTN-1C, by antisense DNA expression, reduced the sensitivity to ER-stressors. In the presence of high RTN-1C levels, genotoxic drugs become ineffective as a consequence of the cytoplasm translocation of p53 protein, while the silencing of endogenous RTN-1C results in the potentiation of the genotoxic drugs action. These data indicate that RTN-1C is able to modulate the cellular sensitivity to different apoptotic pathways representing a promising molecular target for new drug development.

Original languageEnglish
Pages (from-to)345-353
Number of pages9
JournalJournal of Neurochemistry
Volume102
Issue number2
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Endoplasmic Reticulum Stress
Cell death
Neuroblastoma
Cell Death
Switches
Endoplasmic Reticulum
Drug Synergism
Antisense DNA
Apoptosis
Unfolded Protein Response
Proteins
Pharmaceutical Preparations
Protein Transport
Organelles
Cytoplasm
Membranes

Keywords

  • Apoptosis
  • Calcium
  • Endoplasmic reticulum
  • p53
  • Reticulons

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Reticulon-1C acts as a molecular switch between endoplasmic reticulum stress and genotoxic cell death pathway in human neuroblastoma cells. / Sano, Federica D.; Fazi, Barbara; Tufi, Roberta; Nardacci, Roberta; Piacentini, Mauro.

In: Journal of Neurochemistry, Vol. 102, No. 2, 07.2007, p. 345-353.

Research output: Contribution to journalArticle

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