Bax phosphorylation association with nucleus and oligomerization after neonatal Hypoxia-ischemia

Smitha Krishna Infante, Andres F. Oberhauser, J. Regino Perez-Polo

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Neonatal hypoxia-ischemia (HI) is a common occurrence in preterm and low-birth-weight infants, and the incidence of low-birth-weight and preterm births is increasing. Characterization of brain injury after HI is of critical importance in developing new treatments that more accurately target the injury. After severe HI, neuronal cells undergo necrosis and secondary apoptosis of the surrounding cells as a result of neuroinflammation. We sought to characterize the biochemical pathways associated with cell death after HI. Bax, a cell death signaling protein, is activated after HI and translocates to the nucleus, endoplasmic reticulum, and mitochondria. The translocation patterns of Bax affect the resultant cell death phenotype (necrotic or apoptotic) observed. Although Bax is known to oligomerize once it is activated, less is known about the factors that control its translocation and oligomerization. We hypothesize that Bax kinase-specific phosphorylation determines its oligomerization and intracellular localization. Using well-established in vivo and in vitro models of neonatal HI, we characterized Bax oligomerization and multiorganelle translocation. We found that HI-dependent phosphorylation of Bax determines its oligomerization status and multiorganelle localization, and, ultimately, the cell death phenotype observed. Understanding the mechanisms of Bax translocation will aid in the rational design of therapeutic strategies that decrease the trauma resulting from HI-associated inflammation.

Original languageEnglish (US)
Pages (from-to)1152-1164
Number of pages13
JournalJournal of Neuroscience Research
Volume91
Issue number9
DOIs
StatePublished - Sep 1 2013

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Keywords

  • Bax
  • Development
  • Hypoxia
  • Ischemia
  • Phosphorylation
  • Small-weight babies

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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