Non-Scientific Abstract Fatty acids are naturally occurring substances that
are used in a wide variety of cellular processes. For example, fatty acids are the precursors to
phospholipids, the major components of cell membranes. Fatty acids are also broken down within cells for
energy. There are proteins within cells, known as fatty acid-interacting proteins, which facilitate the
cellšs uptake and retention of fatty acids. Little is known about the usage of fatty acid-interacting
proteins in neuronal cells,which are cells of the nervous system. This study investigates fatty
acid-interacting proteins within PC12 cells, cells that model neuronal cells. The goal of this research is
to determine how fatty acid-interacting proteins affect fatty acid uptake and subsequent membrane
biosynthesis within PC12 cells. In our experiments, PC12 cells were manipulated to express certain fatty
acid-interacting proteins in high amounts. Fatty acid uptake and membrane biosynthesis were then measured
in these over-expressing cells and compared to control cells.Our results indicate that over-expression of
fatty acid-interacting proteins increases both fatty acid uptake and membrane biosynthesis. These results
could be used in the development of nerve regeneration techniques and in the treatment of nervous system
disorders where neurite outgrowth is inhibited.
Abstract The
role of fatty acid-interacting protein (FAIPs) families, such as fatty acid transporters, acyl-CoA
synthetases, and fatty acid binding proteins, in fatty acid uptake has been well-studied, predominantly in
adipocytes.However, the effects of FAIPs on fatty acid metabolic processes, particularly membrane
biosynthesis, are not well-known. This research utilized the PC12 cell line, a model cell line that
differentiates similarly to typical neuronal cells, to explore the contribution of FAIPs to the cellular
metabolic process of membrane biosynthesis. PC12 cell lines were developed that individually
over-expressed members of each FAIP family. Fatty acid uptake assays were conducted to ascertain whether
overexpression of an FAIP increases fatty acid uptake in PC12 cells.Assays to determine the extent of
neurite outgrowth in each over-expressing cell line were also performed. The results of these experiments
indicate that over-expression of FATP1, FATP4,ACS1,ACS4, and EFABP does increase both fatty acid uptake
and neurite outgrowth in differentiating PC12 cells. In addition, over-expression of certain FAIPs, namely
FATP4 and ACS4, increases neurite outgrowth to a much greater extent than over-expression of other FAIPs.
These results indirectly show the effect of FAIPs on membrane biosynthesis and imply an important role of
FAIPs in other fatty acid metabolic processes. |