Nuclear clusterin is associated with neuronal apoptosis in the developing rat brain upon ethanol exposure

Nayoung Kim, Jae Y. Han, Gu S. Roh, Hyun J. Kim, Sang S. Kang, Gyeong J. Cho, Jae-Yong Park, Wan S. Choi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Fetal alcohol spectrum disorder (FASD) is often accompanied by reduced brain volumes, reflecting brain cell death induced by ethanol, but the molecular mechanisms were less elucidated. This study was set up to investigate whether clusterin (Clu) was involved in neuronal cell death in developing rats. Methods: Seven-day-old rats were subcutaneously injected with 20% ethanol in normal saline at 3g/kg twice. The upregulation of Clu and cell death was detected by immunohistochemistry, immunofluorescence microscopy, and/or Western blotting. Protein-protein interaction was detected by immunoprecipitation and immunoblotting. To identify the isoform interacting with Bcl-XL, HT22 mouse hippocampal cells were transfected with nuclear Clu(nClu)- or secretory Clu-expressing vector, and confocal microscopy was performed. Clu transcripts were knocked down in primary cortical cells using siRNA. Results: We found that Clu increased in the cerebral cortex following acute ethanol treatment. The Clu upregulation was related to increased cell death, which was assessed by activated caspase-3 and TUNEL staining. The upregulated Clu was a nuclear isoform that was nuclear translocated upon ethanol exposure and interacted with Bcl-XL, mediating apoptosis. Conclusions: This study shows that nClu plays a pro-apoptotic role in ethanol-induced cell death in the developing brain, providing new insights for development of FASD.

Original languageEnglish
Pages (from-to)72-82
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume36
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1
Externally publishedYes

Fingerprint

Clusterin
Rats
Brain
Ethanol
Apoptosis
Cell death
Cell Death
Fetal Alcohol Spectrum Disorders
Protein Isoforms
Up-Regulation
Alcohols
Brain Death
Confocal microscopy
In Situ Nick-End Labeling
Fluorescence Microscopy
Immunoprecipitation
Immunoblotting
Confocal Microscopy
Caspase 3
Cerebral Cortex

Keywords

  • Apoptosis
  • Bcl-XL
  • Cerebral Cortex
  • Clusterin
  • Fetal Alcohol Spectrum Disorder

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Nuclear clusterin is associated with neuronal apoptosis in the developing rat brain upon ethanol exposure. / Kim, Nayoung; Han, Jae Y.; Roh, Gu S.; Kim, Hyun J.; Kang, Sang S.; Cho, Gyeong J.; Park, Jae-Yong; Choi, Wan S.

In: Alcoholism: Clinical and Experimental Research, Vol. 36, No. 1, 01.01.2012, p. 72-82.

Research output: Contribution to journalArticle

Kim, Nayoung ; Han, Jae Y. ; Roh, Gu S. ; Kim, Hyun J. ; Kang, Sang S. ; Cho, Gyeong J. ; Park, Jae-Yong ; Choi, Wan S. / Nuclear clusterin is associated with neuronal apoptosis in the developing rat brain upon ethanol exposure. In: Alcoholism: Clinical and Experimental Research. 2012 ; Vol. 36, No. 1. pp. 72-82.
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