Molecular switching from ubiquitin-proteasome to autophagy pathways in mice stroke model

Xia Liu, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Ryuta Morihara, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The ubiquitin-proteasome system (UPS) and autophagy are two major pathways to degrade misfolded proteins that accumulate under pathological conditions. When UPS is overloaded, the degeneration pathway may switch to autophagy to remove excessive misfolded proteins. However, it is still unclear whether and how this switch occurs during cerebral ischemia. In the present study, transient middle cerebral artery occlusion (tMCAO) resulted in accelerated ubiquitin-positive protein aggregation from 0.5 h of reperfusion in mice brain after 10, 30 or 60 min of tMCAO. In contrast, significant reduction of p62 and induction of LC3-II were observed, peaking at 24 h of reperfusion after 30 and 60 min tMCAO. Western blot analyses showed an increase of BAG3 and HDAC6 at 1 or 24 h of reperfusion that was dependent on the ischemic period. In contract, BAG1 decreased at 24 h of reperfusion after 10, 30 or 60 min of tMCAO after double immunofluorescent colocalization of ubiquitin, HSP70, p62 and BAG3. These data suggest that a switch from UPS to autophagy occurred between 10 and 30 min of cerebral ischemia depending on the BAG1/BAG3 ratio and level of HDAC6.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Autophagy
Proteasome Endopeptidase Complex
Ubiquitin
Middle Cerebral Artery Infarction
Stroke
Reperfusion
Brain Ischemia
Proteins
Contracts
Western Blotting
Brain

Keywords

  • autophagy
  • middle cerebral artery occlusion
  • protein aggregation
  • Ubiquitin-proteasome system
  • ubiquitination

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Molecular switching from ubiquitin-proteasome to autophagy pathways in mice stroke model. / Liu, Xia; Yamashita, Toru; Shang, Jingwei; Shi, Xiaowen; Morihara, Ryuta; Huang, Yong; Sato, Kota; Takemoto, Mami; Hishikawa, Nozomi; Ohta, Yasuyuki; Abe, Koji.

In: Journal of Cerebral Blood Flow and Metabolism, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Shang, Jingwei

AU - Shi, Xiaowen

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AU - Huang, Yong

AU - Sato, Kota

AU - Takemoto, Mami

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AU - Abe, Koji

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