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Changes in proliferating cell nuclear antigen, a protein involved in DNA repair, in vulnerable hippocampal neurons following global cerebral ischemia

Tomasevic, Gregor LU ; Kamme, Fredrik LU and Wieloch, Tadeusz LU (1998) In Molecular Brain Research 60(2). p.168-176
Abstract

Proliferating cell nuclear antigen (PCNA) is required for completion of the DNA synthesis step of DNA replication as well as nucleotide excision repair (NER) of damaged DNA. We investigated the expression of PCNA mRNA and the levels of PCNA protein in the adult rat hippocampus following normo- and hypothermic global forebrain ischemia. Hypothermia protected the CA1 neurons from ischemic damage. A constitutive expression of PCNA mRNA and protein was detected in all hippocampal subfields, as well as in other brain regions. During reperfusion, PCNA mRNA levels were up-regulated in the vulnerable CA1 subfield at 36 h following normothermic ischemia. In hypothermia, this induction appeared already after 18 h. Following normothermic ischemia,... (More)

Proliferating cell nuclear antigen (PCNA) is required for completion of the DNA synthesis step of DNA replication as well as nucleotide excision repair (NER) of damaged DNA. We investigated the expression of PCNA mRNA and the levels of PCNA protein in the adult rat hippocampus following normo- and hypothermic global forebrain ischemia. Hypothermia protected the CA1 neurons from ischemic damage. A constitutive expression of PCNA mRNA and protein was detected in all hippocampal subfields, as well as in other brain regions. During reperfusion, PCNA mRNA levels were up-regulated in the vulnerable CA1 subfield at 36 h following normothermic ischemia. In hypothermia, this induction appeared already after 18 h. Following normothermic ischemia, nuclear PCNA immunoreactivity was largely abolished during reperfusion in the vulnerable CA1 neurons, prior to cell death. In contrast, total PCNA protein content of this region, as measured by Western blotting, remained largely unchanged. In the CA3 region, a transient decrease in nuclear PCNA immunoreactivity was observed. In the dentate gyrus region, no down-regulation of nuclear or total PCNA protein was observed during reperfusion. Following hypothermic ischemia, the PCNA protein levels did not decrease in any of the hippocampal subregions. In contrast, no change in the levels of Ref-1, a protein involved in base excision DNA repair (BER), was observed following normo- or hypothermic ischemia. Our findings indicate an altered functional state of PCNA protein in the ischemia-sensitive CA1 neurons suggesting that DNA repair processes are affected in these post-mitotic cells following ischemia. Impaired DNA repair may play a role in the development of postischemic neuronal damage.

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author
organization
publishing date
type
Contribution to journal
publication status
published
keywords
DNA repair, Global cerebral ischemia, Hypothermia, Proliferating cell nuclear antigen (PCNA), Ref-1
in
Molecular Brain Research
volume
60
issue
2
pages
168 - 176
publisher
Elsevier
external identifiers
  • Scopus:0032189274
ISSN
0169-328X
DOI
10.1016/S0169-328X(98)00173-9
language
English
LU publication?
yes
id
cccb9007-6dc0-43d5-8bc7-9635ab28fe02
date added to LUP
2016-10-05 16:03:42
date last changed
2016-11-29 10:05:22
@misc{cccb9007-6dc0-43d5-8bc7-9635ab28fe02,
  abstract     = {<p>Proliferating cell nuclear antigen (PCNA) is required for completion of the DNA synthesis step of DNA replication as well as nucleotide excision repair (NER) of damaged DNA. We investigated the expression of PCNA mRNA and the levels of PCNA protein in the adult rat hippocampus following normo- and hypothermic global forebrain ischemia. Hypothermia protected the CA1 neurons from ischemic damage. A constitutive expression of PCNA mRNA and protein was detected in all hippocampal subfields, as well as in other brain regions. During reperfusion, PCNA mRNA levels were up-regulated in the vulnerable CA1 subfield at 36 h following normothermic ischemia. In hypothermia, this induction appeared already after 18 h. Following normothermic ischemia, nuclear PCNA immunoreactivity was largely abolished during reperfusion in the vulnerable CA1 neurons, prior to cell death. In contrast, total PCNA protein content of this region, as measured by Western blotting, remained largely unchanged. In the CA3 region, a transient decrease in nuclear PCNA immunoreactivity was observed. In the dentate gyrus region, no down-regulation of nuclear or total PCNA protein was observed during reperfusion. Following hypothermic ischemia, the PCNA protein levels did not decrease in any of the hippocampal subregions. In contrast, no change in the levels of Ref-1, a protein involved in base excision DNA repair (BER), was observed following normo- or hypothermic ischemia. Our findings indicate an altered functional state of PCNA protein in the ischemia-sensitive CA1 neurons suggesting that DNA repair processes are affected in these post-mitotic cells following ischemia. Impaired DNA repair may play a role in the development of postischemic neuronal damage.</p>},
  author       = {Tomasevic, Gregor and Kamme, Fredrik and Wieloch, Tadeusz},
  issn         = {0169-328X},
  keyword      = {DNA repair,Global cerebral ischemia,Hypothermia,Proliferating cell nuclear antigen (PCNA),Ref-1},
  language     = {eng},
  month        = {10},
  number       = {2},
  pages        = {168--176},
  publisher    = {ARRAY(0x81b5870)},
  series       = {Molecular Brain Research},
  title        = {Changes in proliferating cell nuclear antigen, a protein involved in DNA repair, in vulnerable hippocampal neurons following global cerebral ischemia},
  url          = {http://dx.doi.org/10.1016/S0169-328X(98)00173-9},
  volume       = {60},
  year         = {1998},
}