Hypoxia/ischemia up-regulates Id2 expression in neuronal cells in vivo and in vitro

Neurosci Lett. 2013 Oct 25:554:88-93. doi: 10.1016/j.neulet.2013.08.044. Epub 2013 Aug 30.

Abstract

Inhibitor of DNA binding/differentiation 2 (Id2) belongs to a family of transcriptional modulators characterized by a helix-loop-helix (HLH) motif that lacks the basic amino acid domain necessary to bind DNA. The aim of this study was to obtain a better understanding of the role of Id2 in hypoxia/ischemia (H/I)-induced neuronal apoptosis. Following H/I induction in a rat model of middle cerebral artery occlusion (MCAO)/reperfusion, the number of TUNEL-positive cells in cerebral cortices of the penumbra area increased gradually, while the Id2 mRNA and protein expression were also significantly up-regulated. The hypoxia-mimetic, cobalt chloride (CoCl2)-treated rat neuroblastoma B35 cell line also demonstrated enhanced Id2 mRNA and protein expression as well as increased number of cells in the sub-G1 populations after H/I exposure. Consistently, the expression of Bax, a proapoptotic protein, was also up-regulated in vivo and in vitro. Moreover, triple immunofluorescence demonstrated the obvious co-localization of Id2, TUNEL and NeuN in neurons of the penumbra area. These data suggest that H/I up-regulates Id2 expression in neuronal cells, and Id2 might play an important role in H/I-induced neuronal apoptosis.

Keywords: Apoptosis; Hypoxia; Id2; Ischemia; Neuronal cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Hypoxia-Ischemia, Brain / etiology
  • Hypoxia-Ischemia, Brain / metabolism*
  • Hypoxia-Ischemia, Brain / pathology
  • Infarction, Middle Cerebral Artery / complications
  • Inhibitor of Differentiation Protein 2 / genetics
  • Inhibitor of Differentiation Protein 2 / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Id2 protein, rat
  • Inhibitor of Differentiation Protein 2
  • RNA, Messenger
  • bcl-2-Associated X Protein