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Increased expression of cyclin G1 and p21 WAF1/CIP1 in neurons following transient forebrain ischemia: Comparison with early DNA damage
Author(s) -
Campagne Menno van Lookeren,
Gill Ramanjit
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19980801)53:3<279::aid-jnr2>3.0.co;2-7
Subject(s) - striatum , biology , hippocampus , forebrain , dna damage , cyclin d1 , cerebral cortex , microbiology and biotechnology , cortex (anatomy) , cell cycle , dna , endocrinology , cell , central nervous system , neuroscience , biochemistry , dopamine
Oxidative stress affecting DNA integrity may be an important mediator of cell death induced by cerebral ischemia followed by reperfusion. Genes involved in the DNA repair processes may play an important role in cell viability. We studied the spatial expression of the DNA damage inducible gene p53 and its transcriptional targets p21 WAF1/CIP1 , cyclin G1, and Bax and compared their expression with markers of early DNA damage following 10 min of transient forebrain ischemia in rats. Cyclin G1 and p21 WAF1/CIP1 mRNA levels increased significantly between 2.5 and 4‐fold in neurons of the hippocampus, cortex, and striatum during the first 24 hr after reperfusion and decreased at 48 hr of reperfusion. Significant increases in the protein levels of Cyclin G1 and p21 WAF1/CIP1 were only seen in the striatum at 48 hr of reperfusion. The mRNA levels of the p21 family members p27 KIP1 or p57 KIP2 demonstrated no significant changes. p53, bax α, and bcl‐xl mRNA levels increased in all areas of the hippocampus by 12 to 24 hr and decreased over the next 2 days of reperfusion. bax α mRNA was specifically induced in neurons of the outer cortical layers at 12 and 24 hr after reperfusion, and protein levels increased in the striatum at 48 hr. No changes in protein levels of p53, Bcl‐xl, or Bcl‐2 were detected in the cerebral cortex, hippocampus, or striatum at any time point following reperfusion. Single‐stranded DNA breaks detected with DNA polymerase I‐mediated in situ nick translation partly overlapped with nuclear cyclin G1 protein in the striatum, cortex, and hippocampus at 24 hr, however at 48 hr cyclin G1 remained elevated only in neurons bordering areas exhibiting DNA damage. Nuclear p53 protein, p21 mRNA, and bax α mRNA were absent in cells stained with the in situ nick translation method but p21 mRNA and bax α mRNA were increased in neurons adjacent to those with detectable DNA nick ends at 24 and 48 hr following reperfusion. The enhanced expression of cyclin G1, p21 WAF1/CIP1 , and bax α in neurons surviving transient forebrain ischemia may indicate their participation in an adaptive response to cerebral ischemia and reperfusion. J. Neurosci. Res. 53:279–296, 1998. © 1998 Wiley‐Liss, Inc.