Related Experiment Videos
PARP-1-dependent 3-nitrotyrosine protein modification after DNA damage
E Siles1, E Martinez-Lara, M I Núñez
1Dpto. Biología Experimental, Universidad de Jaén, Spain.
Journal of Cellular Biochemistry
|July 30, 2005
Summary
Poly(ADP-ribose)polymerase-1 (PARP-1) influences protein nitration and oxidative stress during DNA damage. PARP-1 deficiency reduces nitrotyrosine formation and mitochondrial injury, suggesting PARP-1 modulates NO-derived damage.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Biology
Background:
- 3-nitrotyrosine (NO2-Tyr) is a marker of oxidative cell injury.
- Poly(ADP-ribose)polymerase-1 (PARP-1) plays a role in DNA damage response.
Purpose of the Study:
- To investigate the role of PARP-1 in protein nitration following DNA damage.
- To assess the impact of PARP-1 deficiency on oxidative stress markers.
Main Methods:
- Treatment of immortalized fibroblasts (parp-1+/+ and parp-1-/-) with 2 -methyl-2 -nitroso-urea (MNU).
- Analysis of inducible nitric oxide synthase (iNOS) expression and protein tyrosine nitration.
- Identification of nitrated proteins and localization of oxidative stress.
Main Results:
- MNU treatment increased iNOS expression and protein nitration in both cell lines.
- PARP-1 deficient cells showed delayed iNOS accumulation and reduced protein nitration.
- Mitochondrial compartment identified as a major site of oxidative stress, with MnSOD being nitrated in parp-1+/+ but not parp-1-/- cells.
Conclusions:
- PARP-1 modulates NO-derived injury and protein nitration.
- PARP-1 deficiency limits oxidative injury, potentially explaining reduced damage in knockout models.
- Proteins involved in genotoxic damage response, like PARP-1, can influence oxidative stress.