Mitochondrial-nuclear p53 trafficking controls neuronal susceptibility in stroke

被引:28
作者
Almeida, Angeles [1 ,2 ]
Sanchez-Moran, Irene [1 ,2 ]
Rodriguez, Cristina [1 ,2 ]
机构
[1] Univ Salamanca, Inst Funct Biol & Genom, CSIC, Salamanca, Spain
[2] Univ Salamanca, Univ Hosp Salamanca, Inst Biomed Res Salamanca, CSIC, Salamanca, Spain
基金
欧盟地平线“2020”;
关键词
apoptosis; functional recovery; mitochondria; neurons; p53; stroke; DNA-BINDING; CELL-DEATH; EXPORT SIGNAL; APOPTOSIS; ACTIVATION; INHIBITION; PATHWAY; DOMAIN; MDM2; ACETYLATION;
D O I
10.1002/iub.2453
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Stroke is a major cause of death and long-term disability in the adult. Neuronal apoptosis plays an essential role in the pathophysiology of ischemic brain damage and impaired functional recovery after stroke. The tumor suppressor protein p53 regulates key cellular processes, including cell cycle arrest, DNA repair, senescence, and apoptosis. Under cellular stress conditions, p53 undergoes post-translational modifications, which control protein localization, stability, and proapoptotic activity. After stroke, p53 rapidly accumulates in the ischemic brain, where it activates neuronal apoptosis through both transcriptional-dependent and -independent programs. Over the last years, subcellular localization of p53 has emerged as an important regulator of ischemia-induced neuronal apoptosis. Upon an ischemic insult, p53 rapidly translocates to the mitochondria and interacts with B-cell lymphoma-2 family proteins, which activate the mitochondrial apoptotic program, with higher efficacy than through its activity as a transcription factor. Moreover, the identification of a human single nucleotide polymorphism at codon 72 of the Tp53 gene that controls p53 mitochondrial localization and cell susceptibility to apoptosis supports the important role of the p53 mitochondrial program in neuronal survival and functional recovery after stroke. In this article, we review the relevance of mitochondrial and nuclear localization of p53 on neuronal susceptibility to cerebral ischemia and its impact on functional outcome of stroke patients.
引用
收藏
页码:582 / 591
页数:10
相关论文
共 69 条
[1]   Inhibition of p53 attenuates ischemic stress-induced activation of astrocytes [J].
Ahn, Kee-Chan ;
MacKenzie, Erin M. ;
Learman, Cameron R. ;
Hall, Tia C. ;
Weaver, Charles L. ;
Dunbar, Gary L. ;
Song, Mee-Sook .
NEUROREPORT, 2015, 26 (14) :862-869
[2]   Oxygen and glucose deprivation induces mitochondrial dysfunction and oxidative stress in neurones but not in astrocytes in primary culture [J].
Almeida, A ;
Delgado-Esteban, M ;
Bolaños, JP ;
Medina, JM .
JOURNAL OF NEUROCHEMISTRY, 2002, 81 (02) :207-217
[3]   Genetic determinants of neuronal vulnerability to apoptosis [J].
Almeida, Angeles .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2013, 70 (01) :71-88
[4]   The p53 Transcriptional Network Influences Microglia Behavior and Neuroinflammation [J].
Aloi, Macarena S. ;
Su, Wei ;
Garden, Gwenn A. .
CRITICAL REVIEWS IN IMMUNOLOGY, 2015, 35 (05) :401-415
[5]   Notch signaling and neuronal death in stroke [J].
Arumugam, Thiruma V. ;
Baik, Sang-Ha ;
Balaganapathy, Priyanka ;
Sobey, Christopher G. ;
Mattson, Mark P. ;
Jo, Dong-Gyu .
PROGRESS IN NEUROBIOLOGY, 2018, 165 :103-116
[6]   Interplay between Notch and p53 promotes neuronal cell death in ischemic stroke [J].
Balaganapathy, Priyanka ;
Baik, Sang-Ha ;
Mallilankaraman, Karthik ;
Sobey, Christopher G. ;
Jo, Dong-Gyu ;
Arumugam, Thiruma V. .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2018, 38 (10) :1781-1795
[7]   Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway [J].
Bang, Scott ;
Kaur, Sandeep ;
Kurokawa, Manabu .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (01)
[8]   MDM2 EXPRESSION IS INDUCED BY WILD TYPE-P53 ACTIVITY [J].
BARAK, Y ;
JUVEN, T ;
HAFFNER, R ;
OREN, M .
EMBO JOURNAL, 1993, 12 (02) :461-468
[9]   Wild type- and mutant p53 proteins in mitochondrial dysfunction: emerging insights in cancer disease [J].
Blandino, Giovanni ;
Valenti, Fabio ;
Sacconi, Andrea ;
Di Agostino, Silvia .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2020, 98 :105-117
[10]   The Rich World of p53 DNA Binding Targets: The Role of DNA Structure [J].
Brazda, Vaclav ;
Fojta, Miroslav .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (22)