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 language | English |
|---|---|
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Molecular switching from ubiquitin-proteasome to autophagy pathways in mice stroke model
AU - Liu, Xia
AU - Yamashita, Toru
AU - Shang, Jingwei
AU - Shi, Xiaowen
AU - Morihara, Ryuta
AU - Huang, Yong
AU - Sato, Kota
AU - Takemoto, Mami
AU - Hishikawa, Nozomi
AU - Ohta, Yasuyuki
AU - Abe, Koji
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - autophagy
KW - middle cerebral artery occlusion
KW - protein aggregation
KW - Ubiquitin-proteasome system
KW - ubiquitination
UR - http://www.scopus.com/inward/record.url?scp=85060519445&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060519445&partnerID=8YFLogxK
U2 - 10.1177/0271678X18810617
DO - 10.1177/0271678X18810617
M3 - Article
AN - SCOPUS:85060519445
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
ER -