Abstract
In the aging process and in most degenerative diseases, the oxidant by-products of cellular metabolism lead to oxidative stress. Oxidative stress plays an important role in switching from cell proliferation to its opposite outcome, cell death. The metabolic pathways in charge of the interconversion and degradation of the polyamines are responsible for oxidant by-products. In the past few years, spermine metabolism has been found closely related to DNA oxidation and apoptosis. Moreover, that the ectopical expression of murine spermine oxidase induced DNA damage in the neuroblastoma cell line, and this was uncoupled with any increase in cell mortality, thus suggests an activation of DNA repair. In this work, we provide new evidence showing that only spermine oxidase overactivity can deliver sub-lethal chronic DNA damage and repair without affecting transcriptional and enzymatic levels of the PA key regulatory enzymes ODC and SSAT. Chronic sub-lethal DNA damage is below the cell cycle arrest induction threshold, but is able to activate apurinic/apyrimidinic endonuclease protein (APE1) and γH2AX. Of therapeutic interest, the chronic sub-lethal DNA damage and activation of the repair processes are in turn responsible for inducing hypersensitivity after exposure to radiation with no induction of adaptive response to damage.
| Original language | English |
|---|---|
| Pages (from-to) | 774-783 |
| Number of pages | 10 |
| Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
| Volume | 1773 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2007 |
Fingerprint
Keywords
- DNA damage
- DNA repair
- Oxidative stress
- Radiation
- Spermine oxidase
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Biophysics
Cite this
Chronic sub-lethal oxidative stress by spermine oxidase overactivity induces continuous DNA repair and hypersensitivity to radiation exposure. / Bianchi, M.; Bellini, A.; Cervelli, M.; Degan, P.; Marcocci, L.; Martini, F.; Scatteia, M.; Mariottini, P.; Amendola, R.
In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1773, No. 6, 06.2007, p. 774-783.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronic sub-lethal oxidative stress by spermine oxidase overactivity induces continuous DNA repair and hypersensitivity to radiation exposure
AU - Bianchi, M.
AU - Bellini, A.
AU - Cervelli, M.
AU - Degan, P.
AU - Marcocci, L.
AU - Martini, F.
AU - Scatteia, M.
AU - Mariottini, P.
AU - Amendola, R.
PY - 2007/6
Y1 - 2007/6
N2 - In the aging process and in most degenerative diseases, the oxidant by-products of cellular metabolism lead to oxidative stress. Oxidative stress plays an important role in switching from cell proliferation to its opposite outcome, cell death. The metabolic pathways in charge of the interconversion and degradation of the polyamines are responsible for oxidant by-products. In the past few years, spermine metabolism has been found closely related to DNA oxidation and apoptosis. Moreover, that the ectopical expression of murine spermine oxidase induced DNA damage in the neuroblastoma cell line, and this was uncoupled with any increase in cell mortality, thus suggests an activation of DNA repair. In this work, we provide new evidence showing that only spermine oxidase overactivity can deliver sub-lethal chronic DNA damage and repair without affecting transcriptional and enzymatic levels of the PA key regulatory enzymes ODC and SSAT. Chronic sub-lethal DNA damage is below the cell cycle arrest induction threshold, but is able to activate apurinic/apyrimidinic endonuclease protein (APE1) and γH2AX. Of therapeutic interest, the chronic sub-lethal DNA damage and activation of the repair processes are in turn responsible for inducing hypersensitivity after exposure to radiation with no induction of adaptive response to damage.
AB - In the aging process and in most degenerative diseases, the oxidant by-products of cellular metabolism lead to oxidative stress. Oxidative stress plays an important role in switching from cell proliferation to its opposite outcome, cell death. The metabolic pathways in charge of the interconversion and degradation of the polyamines are responsible for oxidant by-products. In the past few years, spermine metabolism has been found closely related to DNA oxidation and apoptosis. Moreover, that the ectopical expression of murine spermine oxidase induced DNA damage in the neuroblastoma cell line, and this was uncoupled with any increase in cell mortality, thus suggests an activation of DNA repair. In this work, we provide new evidence showing that only spermine oxidase overactivity can deliver sub-lethal chronic DNA damage and repair without affecting transcriptional and enzymatic levels of the PA key regulatory enzymes ODC and SSAT. Chronic sub-lethal DNA damage is below the cell cycle arrest induction threshold, but is able to activate apurinic/apyrimidinic endonuclease protein (APE1) and γH2AX. Of therapeutic interest, the chronic sub-lethal DNA damage and activation of the repair processes are in turn responsible for inducing hypersensitivity after exposure to radiation with no induction of adaptive response to damage.
KW - DNA damage
KW - DNA repair
KW - Oxidative stress
KW - Radiation
KW - Spermine oxidase
UR - http://www.scopus.com/inward/record.url?scp=34249748927&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249748927&partnerID=8YFLogxK
U2 - 10.1016/j.bbamcr.2007.01.014
DO - 10.1016/j.bbamcr.2007.01.014
M3 - Article
C2 - 17363080
AN - SCOPUS:34249748927
VL - 1773
SP - 774
EP - 783
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 6
ER -