Overexpression of Bcl-xl protects septal neurons from prolonged hypoglycemia and from acute ischemia-like stress

K. S. Panickar, D. Nonner, J. N. Barrett

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Overexpression of Bcl-xl, a member of the Bcl-2 protein family, is reported to protect from a variety of stresses involving delayed cell death. We tested the ability of Bcl-xl overexpression to protect primary cultures of embryonic rat septal neurons subjected to one of four different stresses: 6 h of combined oxygen-glucose deprivation, which produces rapid cell death, or a 24 h exposure to hypoglycemia, hyperglycemia, or 1mM 3-nitropropionic acid (an inhibitor of mitochondrial respiration), which results in a more slowly-developing death. Prior to the stress neurons were transiently transfected to overexpress either green fluorescent protein only or green fluorescent protein along with wild-type Bcl-xl. Immediately after oxygen-glucose deprivation, many neurons expressing green fluorescent protein only showed process blebbing and disintegration, with only 49% of the initial cells remaining intact with processes. Neurons expressing both green fluorescent protein and Bcl-xl showed less damage (68% intact post-stress, P<0.05). This result indicates that Bcl-xl's saving effects are not due solely to blocking delayed (apoptotic) death, because death following oxygen-glucose deprivation was rapid and was not accompanied by increased activation of caspase-3. Bcl-xl expression also significantly protected against the hypoglycemic stress (23% intact 24 h post-stress with green fluorescent protein only, compared with 70% with Bcl-xl and green fluorescent protein), but did not protect from hyperglycemia or 3-nitropropionic acid. Thus Bcl-xl does not protect against all forms of delayed death. Bcl-xl's protective effects may include blocking early damaging events, perhaps by increasing mitochondrial function in the face of low levels of energy substrates. Bcl-xl's protective effects may require an intact electron transport chain.

Original languageEnglish (US)
Pages (from-to)73-80
Number of pages8
JournalNeuroscience
Volume135
Issue number1
DOIs
StatePublished - Sep 7 2005

Keywords

  • Bcl-xl
  • Hyperglycemia
  • Hypoglycemia
  • Ischemia
  • Neuron
  • Transfection

ASJC Scopus subject areas

  • Neuroscience(all)

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