Proteomic characterization of an isolated fraction of synthetic proteasome inhibitor (PSI)-induced inclusions in PC12 cells might offer clues to aggresomes as a cellular defensive response against proteasome inhibition by PSI.
BACKGROUND
Cooperation of constituents of the ubiquitin proteasome system (UPS) with chaperone proteins in degrading proteins mediate a wide range of cellular processes, such as synaptic function and neurotransmission, gene transcription, protein trafficking, mitochondrial function and metabolism, antioxidant defence mechanisms, and apoptotic signal transduction. It is supposed that constituents of the UPS and chaperone proteins are recruited into aggresomes where aberrant and potentially cytotoxic proteins may be sequestered in an inactive form.


RESULTS
To determinate the proteomic pattern of synthetic proteasome inhibitor (PSI)-induced inclusions in PC12 cells after proteasome inhibition by PSI, we analyzed a fraction of PSI-induced inclusions. A proteomic feature of the isolated fraction was characterized by identification of fifty six proteins including twenty previously reported protein components of Lewy bodies, twenty eight newly identified proteins and eight unknown proteins. These proteins, most of which were recognized as a profile of proteins within cellular processes mediated by the UPS, a profile of constituents of the UPS and a profile of chaperone proteins, are classed into at least nine accepted categories. In addition, prolyl-4-hydroxylase beta polypeptide, an endoplasmic reticulum member of the protein disulfide isomerase family, was validated in the developmental process of PSI-induced inclusions in the cells.


CONCLUSIONS
It is speculated that proteomic characterization of an isolated fraction of PSI-induced inclusions in PC12 cells might offer clues to appearance of aggresomes serving as a cellular defensive response against proteasome inhibition.
Li
Xing'an
X
Department of Neurology, The First Affiliated Hospital, Jilin University, Changchun, China.
Zhang
Yingjiu
Y
Xie
Peng
P
Piao
Jinhua
J
Hu
Yihong
Y
Chang
Ming
M
Liu
Tao
T
Hu
Linsen
L
D000818:Animals; D002470:Cell Survival; D015180:Electrophoresis, Gel, Two-Dimensional; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016716:PC12 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D040901:Proteomics; D051381:Rats; D015203:Reproducibility of Results
D009419:Nerve Tissue Proteins; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex