Stat3 mediates LIF-induced protection of astrocytes against toxic ROS by upregulating the UPC2 mRNA pool

Daniel W. Lapp, Samuel S. Zhang, Colin Barnstable

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) have been implicated in various types of CNS damage, including stroke. We used a cultured astrocyte model to explore mechanisms of survival of CNS cells following ROS damage. We found that pretreatment with leukemia inhibitory factor (LIF) preserves astrocytes exposed to toxic levels of t-BHP by inhibiting an increase in intracellular ROS following t-BHP treatment. Astrocytes lacking functional Stat3 did not benefit from the pro-survival or antioxidant effects of LIF. Inhibition of mitochondrial uncoupling protein 2 (UCP2) using a chemical inhibitor or siRNA abrogates the prosurvival effects of LIF, indicating a critical role for UCP2 in modulation of mitochondrial ROS production in survival following ROS exposure. LIF treatment of astrocytes results in increased UCP2 mRNA that is accompanied by an increase in Stat3 binding to the UCP2 promoter region. Although treatment with LIF alone did not increase UCP2 protein, a combination of LIF treatment and ROS stress led to increased UCP2 protein levels. We conclude that LIF protects astrocytes from ROS-induced death by increasing UCP2 mRNA, allowing cells to respond to ROS stress by rapidly producing UCP2 protein that ultimately decreases endogenous mitochondrial ROS production.

Original languageEnglish (US)
Pages (from-to)159-170
Number of pages12
JournalGLIA
Volume62
Issue number2
DOIs
StatePublished - Feb 1 2014

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Leukemia Inhibitory Factor
Poisons
Astrocytes
Reactive Oxygen Species
Messenger RNA
Proteins
Uncoupling Protein 2
Genetic Promoter Regions
Small Interfering RNA
Cell Survival
Antioxidants
Stroke

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

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Stat3 mediates LIF-induced protection of astrocytes against toxic ROS by upregulating the UPC2 mRNA pool. / Lapp, Daniel W.; Zhang, Samuel S.; Barnstable, Colin.

In: GLIA, Vol. 62, No. 2, 01.02.2014, p. 159-170.

Research output: Contribution to journalArticle

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