Biology Reference
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modified peptides corresponding to the C-terminal sequence of the
C5a anaphylatoxin have been developed and tested as potent antago-
nists of binding to the C5a receptor. Great promise has been shown
by a potent, chemically synthesized C5a antagonist developed by
Dr. S. M. Taylor's group (AcF-[OPdChaWR]) [50,51]. This cyclic hexa-
peptide has been successfully used as a selective inhibitor of
C5a-mediated functions in animal models of disease and as a means to
discern the involvement of C5a in several pathophysiological processes.
In C5aR blockade studies using the acetylated species of the antagonist,
it was demonstrated that C5aR is critically involved in the development
of sepsis [52], in liver regeneration [53], and in fetal loss associated with
the antiphospholipid antibody syndrome [54]. Recently, this antagonist
was also used in blockade studies that demonstrated an essential role
of C5a in the modulation of CD8 +
T-cell responses during acute
influenza infection in mice [55].
Proteomic Approaches for Studying Protein-Protein Interactions
and Profiling Global Protein Expression
Proteomics is the study of the protein content (“proteome”) of an
organism or a given tissue sample [56]. The basic principle relies on
separating a complex protein/peptide mixture into its components and
then analyzing quantitative changes or identifying certain proteins of
interest. The information about a cell's proteome at a specific time
point can then be correlated with the genomic approach that has been
successfully applied to the study of cell physiology in recent years.
Furthermore, the proteome contains additional functional information
about the investigated tissue or cells that cannot be retrieved from
the corresponding genome or transcriptome (e.g., posttranslational
modifications of proteins) [57].
Appreciating the vast capabilities offered by this novel, high-
throughput technology in global protein expression profiling, our
laboratory has pursued a proteomic analysis of liver regeneration, in an
effort to identify crucial signaling pathways, and changes in acute-
phase response and lipid metabolism after partial hepatectomy in mice.
Liver regeneration is a complex physiological process that recruits
multiple and redundant molecular pathways in order to ensure effec-
tive restoration of the hepatic architecture and function [58]. Identifying
hepatocellular targets that are subject to posttranslational modifications
and could thereby modulate or enhance the regenerative potential of
the liver is of great therapeutic benefit for liver transplant recipients and
living donors. In this respect, a recent study using a broad-range pro-
teomic approach, coupled to mass spectrometry, has identified several
proteins, including acute-phase and metabolic gene products, that are
noticeably affected during liver regeneration [59]. Future investigations
will address the functional relevance of the identified proteins for the
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