Genetic deficiency of the tumor suppressor protein p53 influences erythrocyte survival Academic Article uri icon

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abstract

  • The transcription factor p53 suppresses tumor growth by inducing nucleated cell apoptosis and cycle arrest. Because of its influence on primitive erythroid cell differentiation and survival, p53 is an important determinant of erythropoiesis. However, the impact of p53 on the fate of erythrocytes, cells lacking nucleus and mitochondria, during their post-maturation phase in the circulation remained elusive. Erythrocyte survival may be compromised by suicidal erythrocyte death or eryptosis, which is hallmarked by phosphatidylserine translocation and stimulated by increase of cytosolic Ca2+ concentration. Here, we comparatively examined erythrocyte homeostasis in p53-mutant mice (Trp53tm1Tyj/J) and in corresponding WT mice (C57BL/6J) by analyzing eryptosis and erythropoiesis. To this end, spontaneous cell membrane phosphatidylserine exposure and cytosolic Ca2+ concentration were higher in erythrocytes drawn from Trp53tm1Tyj/J mice than from WT mice. Eryptosis induced by glucose deprivation, a pathophysiological cell stressor, was slightly, but significantly more prominent in erythrocytes drawn from Trp53tm1Tyj/J mice as compared to WT mice. The loss of erythrocytes by eryptosis was fully compensated by enhanced erythropoiesis in Trp53tm1Tyj/J mice, as reflected by increased reticulocytosis and abundance of erythroid precursor cells in the bone marrow. Accordingly, erythrocyte number, packed cell volume and hemoglobin were similar in Trp53tm1Tyj/J and WT mice. Taken together, functional p53 deficiency enhances the turnover of circulating erythrocytes by parallel increase of eryptosis and stimulated compensatory erythropoiesis.

authors

  • Bissinger, Rosi
  • Lang, Elisabeth
  • Gonzalez-Menendez, Irene
  • Quintanilla-Martinez, Leticia
  • Ghashghaeinia, Mehrdad
  • Pelzl, Lisann
  • Sukkar, Basma
  • Bhuyan, Abdulla Al Mamun
  • Salker, Madhuri S
  • Singh, Yogesh
  • Fehrenbacher, Birgit
  • Fakhri, Hajar
  • Umbach, Anja T
  • Schaller, Martin
  • Qadri, Syed
  • Lang, Florian

publication date

  • December 2018