| RRC ID |
87261
|
| 著者 |
Watanabe K, Shibuya S, Ozawa Y, Toda T, Shimizu T.
|
| タイトル |
Pathological Relationship between Intracellular Superoxide Metabolism and p53 Signaling in Mice.
|
| ジャーナル |
Int J Mol Sci
|
| Abstract |
Intracellular superoxide dismutases (SODs) maintain tissue homeostasis via superoxide metabolism. We previously reported that intracellular reactive oxygen species (ROS), including superoxide accumulation caused by cytoplasmic SOD (SOD1) or mitochondrial SOD (SOD2) insufficiency, induced p53 activation in cells. SOD1 loss also induced several age-related pathological changes associated with increased oxidative molecules in mice. To evaluate the contribution of p53 activation for SOD1 knockout (KO) (Sod1-/-) mice, we generated SOD1 and p53 KO (double-knockout (DKO)) mice. DKO fibroblasts showed increased cell viability with decreased apoptosis compared with Sod1-/- fibroblasts. In vivo experiments revealed that p53 insufficiency was not a great contributor to aging-like tissue changes but accelerated tumorigenesis in Sod1-/- mice. Furthermore, p53 loss failed to improve dilated cardiomyopathy or the survival in heart-specific SOD2 conditional KO mice. These data indicated that p53 regulated ROS-mediated apoptotic cell death and tumorigenesis but not ROS-mediated tissue degeneration in SOD-deficient models.
|
| 巻・号 |
22(7)
|
| 公開日 |
2021-3-29
|
| DOI |
10.3390/ijms22073548
|
| PII |
ijms22073548
|
| PMID |
33805584
|
| PMC |
PMC8037821
|
| MeSH |
Animals
Apoptosis / genetics
Female
Fibroblasts / metabolism
Heart / physiopathology
Male
Mice
Mice, Knockout
Mice, Transgenic
Neoplasms / genetics
Phenotype
Signal Transduction / genetics
Superoxide Dismutase / genetics
Superoxide Dismutase / metabolism
Superoxide Dismutase 2
Superoxide Dismutase-1 / genetics
Superoxide Dismutase-1 / metabolism
Superoxides / metabolism*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
|
| リソース情報 |
| 実験動物マウス |
RBRC01361 |
