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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 2013

Fingerprint

Ischemia
Phosphorylation
Cell Death
Premature Birth
Low Birth Weight Infant
Phenotype
Hypoxia
Wounds and Injuries
Endoplasmic Reticulum
Brain Injuries
Mitochondria
Necrosis
Phosphotransferases
Apoptosis
Inflammation
Incidence
Therapeutics
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Bax phosphorylation association with nucleus and oligomerization after neonatal Hypoxia-ischemia. / Infante, Smitha Krishna; Oberhauser, Andres; Perez-Polo, J. Regino.

In: Journal of Neuroscience Research, Vol. 91, No. 9, 09.2013, p. 1152-1164.

Research output: Contribution to journalArticle

@article{507fe6dce7244640b066f883a97eb064,
title = "Bax phosphorylation association with nucleus and oligomerization after neonatal Hypoxia-ischemia",
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.",
keywords = "Bax, Development, Hypoxia, Ischemia, Phosphorylation, Small-weight babies",
author = "Infante, {Smitha Krishna} and Andres Oberhauser and Perez-Polo, {J. Regino}",
year = "2013",
month = "9",
doi = "10.1002/jnr.23224",
language = "English (US)",
volume = "91",
pages = "1152--1164",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Bax phosphorylation association with nucleus and oligomerization after neonatal Hypoxia-ischemia

AU - Infante, Smitha Krishna

AU - Oberhauser, Andres

AU - Perez-Polo, J. Regino

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - Bax

KW - Development

KW - Hypoxia

KW - Ischemia

KW - Phosphorylation

KW - Small-weight babies

UR - http://www.scopus.com/inward/record.url?scp=84880508086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880508086&partnerID=8YFLogxK

U2 - 10.1002/jnr.23224

DO - 10.1002/jnr.23224

M3 - Article

C2 - 23861070

AN - SCOPUS:84880508086

VL - 91

SP - 1152

EP - 1164

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 9

ER -