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Decreased expression of sirtuin 6 is associated with release of high mobility group box-1 after cerebral ischemia.

Abstract
Sirtuin 6 (SIRT6) belongs to the sirtuin family of NAD(+)-dependent deacetylases and has been implicated in the regulation of metabolism, inflammation, and aging. Here, we found that SIRT6 was predominantly expressed in neuronal cells throughout the entire brain. Ischemia models using transient middle cerebral artery occlusion in rats and oxygen/glucose deprivation (OGD) in SH-SY5Y neuronal cells showed that ischemia reduced SIRT6 expression and induced the release of high mobility group box-1 (HMGB1) from cell nuclei. The reduced expression of SIRT6 via treatment with SIRT6 siRNA dramatically enhanced the OGD-induced release of HMGB1 in SH-SY5Y cells. Together, our data suggest that SIRT6 may serve as a potential therapeutic target for HMGB1-mediated inflammation after cerebral ischemia.
AuthorsOk-Hee Lee, Jayoung Kim, Jin-Moo Kim, Hyunji Lee, Eun Hee Kim, Soo-Kyung Bae, Youngsok Choi, Hyo Suk Nam, Ji Hoe Heo
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 438 Issue 2 Pg. 388-94 (Aug 23 2013) ISSN: 1090-2104 [Electronic] United States
PMID23899523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • HMGB1 Protein
  • RNA, Small Interfering
  • Sirtuins
  • sirtuin 6, rat
  • Glucose
  • Oxygen
Topics
  • Animals
  • Brain (cytology, metabolism)
  • Brain Ischemia (metabolism)
  • Cell Death
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Glucose (metabolism)
  • HEK293 Cells
  • HMGB1 Protein (metabolism)
  • Humans
  • Inflammation
  • Male
  • Middle Cerebral Artery (pathology)
  • Neurons (metabolism)
  • Oxygen (metabolism)
  • RNA, Small Interfering (metabolism)
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Sirtuins (metabolism)

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