ASCB 2013 PressBook - page 5

T H E A M E R I C A N S O C I E T Y F O R C E L L B I O L O G Y
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5
News from
The American Society
for Cell Biology
53rd Annual Meeting
New Orleans, LA
December 14–18, 2013
Going up in steam?
EMBARGOED
FOR RELEASE
10:00 am, U.S. Central Time
Sunday, December 15, 2013
Contact
Chi-Ming Hai
Professor of Medical Science
Department of Molecular
Pharmacology, Physiology
& Biotechnology
Brown University
Box G-B3
171 Meeting Street
Providence, RI 02912
(401) 863-3288
Author Presents
Sunday, December 15
1:30 PM–3:00 PM
Focal Adhesions and Invadosomes
Presentation 677
Poster B1204
Exhibit Halls B–D
Nicotine induces invadosome
formation and cell invasion in
A7r5 and primary human
vascular smooth muscle cells
C-M. Hai

Molecular Pharmacology,
Physiology & Biotechnology,
Brown University, Providence,
Rhode Island
This study was supported by
a research grant (HL52714)
from the NIH National Heart,
Lung, and Blood Institute.
Nicotine drives cell invasion in
vascular muscle cells, which
contributes to plaque formation
in atherosclerosis
E
-cigarettes have put nicotine back
in the news and into the hands of a
growing number of American smok-
ers who now “vape,” that is, inhale a steam
of nicotine, polyethylene glucose (PEG), and
flavoring generated by cigarette-shaped,
battery-powered vaporizers.
E-cigarettes are being promoted as
“safe” nicotine delivery systems even though
the safety of nicotine, the key addictive
substance in tobacco smoke, is disputed,
partly because the mechanism by which it
acts on the circulatory system has not been
well understood. Now a nicotine researcher
at Brown University, Chi-Ming Hai, pres-
ents evidence from human and rat vascular
smooth muscle cells that shows a link be-
tween nicotine and atherosclerosis.
In Hai’s experiments, nicotine appeared
to drive the formation of a kind of cellular
drill called podosome rosettes, which are
members of the invadosome family, consist-
ing of invadopodia, podosomes, and podo-
some rosettes. These are specialized cell
surface assemblies that degrade and pen-
etrate the tissue during cell invasion. Inva-
sion of vascular smooth muscle cells from
the middle layer of the arterial wall (media)
to the inner layer of the arterial wall (intima)
contributes substantially to plaque forma-
tion in atherosclerosis.
Hai subjected rat and primary human
vascular smooth muscle cells to prolonged
(six hours) nicotine treatment, enabling the
cells to form podosome rosettes in response
to protein kinase C (PKC) activation, which
controls protein phosphorylation in sig-
nal transduction cascades. The podosome
rosettes set the scene for global extracellular
matrix degradation and internalization.
PKC activation alone, that is, without nico-
tine treatment, could induce the forma-
tion of podosomes in the rat muscle cells,
accompanied by focal extracellular matrix
degradation.
Nicotinic acetylcholine receptors,
which bind neurotransmitters, co-localized
with other podosome markers (vinculin,
PKC-alpha, and metalloproteinase-2) at
podosomes and podosome rosettes in the
rat cells. Matrigel-coated transwell experi-
ments indicated that nicotine treatment
and PKC activation worked synergistically
to enhance invasiveness in the primary
human vascular smooth muscle cells.
Inclusion of alpha-bungarotoxin, a nico-
tinic acetylcholine receptor antagonist, or
cycloheximide, a protein synthesis inhibi-
tor, during nicotine treatment abolished
nicotine-induced podosome rosette forma-
tion in the rat cells, suggesting that signal-
ing through the nicotinic acetylcholine
receptors and synthesis of new proteins are
required for podosome rosette formation.
Altogether, the data acquired from rat and
primary human vascular smooth muscle
cells suggest that nicotine enhances vascu-
lar smooth muscle cell invasion by activat-
ing synergistic mechanisms between the
nicotinic acetylcholine receptor and PKC
signaling.
According to Hai, a potential clinical
implication of findings from this study is
that replacing cigarette smoking by nico-
tine administration may not bring much
benefit to lowering the risk of develop-
ing atherosclerosis. Still, Hai believes that
understanding the synergistic mechanisms
between nicotinic acetylcholine receptor
and PKC in vascular smooth muscle inva-
sion may lead to new therapeutics for
minimizing the damaging effects of
nicotine on the vascular system.
Vascular smooth muscle cell invasion from media to
intima contributes substantially to plaque formation in
atherosclerosis.
Nicotine enables vascular smooth muscle cell to form
invasive structure (podosome rosette) in response to
PKC activation.
I,II,1,2,3,4 6,7,8,9,10,11,12,13
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