{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:28:08Z","timestamp":1790486888896,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2212\/\u2212) mice, we generated SOD1 and p53 KO (double-knockout (DKO)) mice. DKO fibroblasts showed increased cell viability with decreased apoptosis compared with Sod1\u2212\/\u2212 fibroblasts. In vivo experiments revealed that p53 insufficiency was not a great contributor to aging-like tissue changes but accelerated tumorigenesis in Sod1\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms22073548","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T16:01:57Z","timestamp":1617033717000},"page":"3548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pathological Relationship between Intracellular Superoxide Metabolism and p53 Signaling in Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-1676","authenticated-orcid":false,"given":"Kenji","family":"Watanabe","sequence":"first","affiliation":[{"name":"Aging Stress Response Research Project Team, National Center for Geriatrics and Gerontology, Obu 474-8511, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Shibuya","sequence":"additional","affiliation":[{"name":"Aging Stress Response Research Project Team, National Center for Geriatrics and Gerontology, Obu 474-8511, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba 260-8677, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2522-9699","authenticated-orcid":false,"given":"Toshihiko","family":"Toda","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba 260-8677, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3351-3342","authenticated-orcid":false,"given":"Takahiko","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Aging Stress Response Research Project Team, National Center for Geriatrics and Gerontology, Obu 474-8511, Aichi, Japan"},{"name":"Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba 260-8677, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140165","DOI":"10.1155\/2014\/140165","article-title":"Superoxide dismutase 1 loss disturbs intracellular redox signaling, resulting in global age-related pathological changes","volume":"2014","author":"Watanabe","year":"2014","journal-title":"Biomed. 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