For Journalists
Working with CPA
About the University
Contact News & Media Relations Staff
Featured Events
Calendar
Facility Rental
Join Our Mailing List
Contact Events Staff
University Publications
Publications Opt-Out
Public Awareness
Scientific Animations
Contact Marketing Communications Staff
 |
Saturday, August 30, 2008 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Current issue
How bad cholesterol gets worse
BY KRISTINE KELLY
Last spring, Kara Maxwell, a biomedical fellow
in Jan Breslow’s Laboratory of Biochemical Genetics and
Metabolism, showed that she could increase levels of LDL
cholesterol (the “bad” kind) in mice by increasing the
expression of a gene called PCSK9. Now, results from
a new paper published in Proceedings of
the National Academy of Sciences show
how that happens.
Maxwell and Breslow experimented on human
liver cancer cells, which they engineered to overexpress PCSK9. The
extra PCSK9 caused the cells to lose their LDL receptors, which
normally serve to soak up LDL cholesterol from the bloodstream.
Though normal numbers of LDL receptors were manufactured, the
receptor was being destroyed as it made its way to the surface of
the cell.
The team’s findings complement a recent
human population study in which investigators at the University of
Texas Southwestern Medical Center found that about 2 percent of
African-Americans with low LDL levels have mutations in the PCSK9
gene that disable the protein. Thus a picture has emerged in which
too much PCSK9 decreases LDL receptors and raises LDL cholesterol
levels, and too little PCSK9 does the opposite. The two papers were
cited in Science magazine as the Editor’s Choice in Biomedicine
for the February 11th 2005 issue.
Previous studies of LDL receptor regulation
focused on how the receptor’s gene was turned on and off.
“It is now clear that other genes are capable of regulating
LDL receptors by different mechanisms, and LDL cholesterol lowering
strategies of the future may target these genes,” says
Breslow. “For example, an inhibitor of PCSK9 might act to
increase liver LDL receptors and lower blood LDL cholesterol
levels.”
“At this point, we don’t know the
exact mechanism by which PCSK9 degrades the LDL receptor,”
says Maxwell. “We are working on understanding whether PCSK9
directly destroys the receptor, or if it destroys another protein
essential for the LDL receptor’s integrity. We are also
developing tools to prevent PCSK9 from destroying the LDL receptor
as a way to decrease blood LDL cholesterol levels.”
March 18, 2005
|
|
 |
Archive Search
|
|
Editor
Zach Veilleux
Science Writers
Lauren Gravitz
Kristine Kelly
Assistant Editor
Talley Henning Brown
Art Direction
Bolle Design, NYC
Copyright © 2006
The Rockefeller University
|
Archive:
2005 2004 2003 2001-2002 1999-2000
|
|
|
|
|
|
|
|
|
|
|
|
