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 language | English |
|---|---|
| Pages (from-to) | 345-353 |
| Number of pages | 9 |
| Journal | Journal of Neurochemistry |
| Volume | 102 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jul 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Reticulon-1C acts as a molecular switch between endoplasmic reticulum stress and genotoxic cell death pathway in human neuroblastoma cells
AU - Sano, Federica D.
AU - Fazi, Barbara
AU - Tufi, Roberta
AU - Nardacci, Roberta
AU - Piacentini, Mauro
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Calcium
KW - Endoplasmic reticulum
KW - p53
KW - Reticulons
UR - http://www.scopus.com/inward/record.url?scp=34347230960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34347230960&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2007.04479.x
DO - 10.1111/j.1471-4159.2007.04479.x
M3 - Article
C2 - 17596210
AN - SCOPUS:34347230960
VL - 102
SP - 345
EP - 353
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -