Comparative analysis of brain proteins from p53-deficient mice by two-dimensional electrophoresis

Electrophoresis. 2000 May;21(9):1880-9. doi: 10.1002/(SICI)1522-2683(20000501)21:9<1880::AID-ELPS1880>3.0.CO;2-9.

Abstract

p53 is a tumor suppressor protein that regulates many cellular processes including the cell cycle, DNA repair, and apoptosis. It also serves as a critical regulator of neuronal apoptosis in the central nervous system (CNS). To elucidate the role of p53 in the CNS, brain proteins of p53 knock-out mice (p53-/-) were analyzed by two-dimensional gel electrophoresis (2-DE) and compared with those from p53 wild type (p53+/+) mice. Six types of brain tissue (temporal cortex, cerebellum, hippocampus, striatum, olfactory bulb, and cervical spinal cord) and other control tissues (lung and blood) from 18-week-old non-stress-induced mice were analyzed. The morphology of brains from p53-/- mice appeared to be normal and identical to that of p53+/+ mice, although lungs showed diffuse tumors that may have been caused by p53 deficiency. Comparative 2-D gel analysis showed that, on average, 7 of 886 spots from brain tissue were p53-/- specific, whereas 12 of 1008 spots from lung tissue were p53-/- specific. N-terminal amino acid sequence was determined for p53-/- specific proteins. In all brain tissues from p53-/- mice, a newly identified mouse mitochondrial NADH-ubiquinone oxidoreductase 24 kDa subunit showed decreased expression, and apolipoprotein A1 acidic forms showed increased expression. In addition, brain-type creatine kinase B chain and tubulin beta-5 N-terminal fragment were increased in the p53-/- cerebellum, and a new protein in mouse, hydroxyacylglutathione hydrolase (glyoxalase II) was decreased in the temporal cortex of p53-/- mice. The alterations in protein expression identified in this study may imply a p53-related brain function. This is the first proteomic analysis on the p53-/- mouse brain, and further information based on this study will provide new insights into the p53 function in the CNS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apolipoprotein A-I / metabolism
  • Brain / metabolism*
  • Creatine Kinase / metabolism
  • Electron Transport Complex I
  • Electrophoresis, Gel, Two-Dimensional / methods
  • Male
  • Mice
  • Mice, Inbred CBA
  • Mice, Knockout
  • Molecular Sequence Data
  • NADH, NADPH Oxidoreductases / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Thiolester Hydrolases / metabolism
  • Tubulin / metabolism
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Apolipoprotein A-I
  • Nerve Tissue Proteins
  • Tubulin
  • Tumor Suppressor Protein p53
  • NADH, NADPH Oxidoreductases
  • Creatine Kinase
  • Thiolester Hydrolases
  • hydroxyacylglutathione hydrolase
  • Electron Transport Complex I