Characterization of proteasome inhibition on astrocytes cell cycle.
Increasing evidence indicates that proteasome inhibition occurs in multiple central nervous system (CNS) disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Compared with the extensive studies on neurons, little attention is paid on the proteasome inhibition in astrocytes. Here, we demonstrated that lactacystin inhibited proteasome dose-dependently in cultured astrocytes. Simultaneously, lactacystin suppressed the expression of cell cycle proteins in astrocytes and caused the proliferating astrocytes arrested at G1/S checkpoint. Western blots showed that proteasome inhibition led to a decrease in cdk-2, cdk-4, cyclin D1 expression accompanied with an increase in p21waf1/cip1 expression. The effect of chronic low-level proteasome inhibition on astrocytes was consistent with that in acute proteasome inhibition. Furthermore, increased levels of interleukin-6 (IL-6) secretion, STAT-3 and phospho-STAT-3 expression were found, suggesting that proteasome inhibition in astrocytes could stabilize signals of grow arrest through the JAK/STAT signaling cascade.
Ren
Qing-Guo
QG
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Yu
Ying
Y
Luo
Xiang
X
Jie
Xie-Min
XM
Pan
Deng-Ji
DJ
Wang
Wei
W
D000111:Acetylcysteine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D061988:Proteasome Inhibitors; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D018797:Cell Cycle Proteins; D015853:Cysteine Proteinase Inhibitors; D015850:Interleukin-6; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C067713:lactacystin; D000111:Acetylcysteine