Download Differential effects of n-3 polyunsaturated fatty acids on tendon

Biochemical Society Transactions (2002) Volume 30, Part 6
15 Transgenic wheat lines mimicking metabolic responses to the
Greenhouse effect.
T. Beacham, D. Edlin, P. Kille, and J.L. Harwood
School of Biosciences, Cardiff University, PO Box 911,
Card# CFlO 3US, Wales, U.K.
Current predictions suggest C 0 2 concentrations will approximately
double to 650 p . p m and that temperature will rise by an average of
4 "C by the middle of the century. These Greenhouse conditions significantly affect wheat lipid metabolism. It is proposed that these
metabolic changes are due to altered activity of two key enzymes:
glycerol 3-phosphate acyltransferase and acyl-ACP thioesterase. The
substrate specificities and relative activities of these two enzyme
systems determines the fate of newly formed fatty acids in the
chloroplast. Transgenic lines were created containing either a Pisum
sativum (pea) glycerol %phosphate acyltransferase gene, o r an
Arabidopsis thaliana acyl-ACP thioesterase gene, singularly o r in
combination. Plants transformed with the pea acyltransferase
contained more mitochondria and chloroplasts than non-transformed wheat and also exhibited significantly larger chloroplasts.
Preliminary results indicate a significant alteration in growth rate in
lines transformed with pea glycerol 3-phosphate acyltransferase o n
its own o r in combination with the Arabidopsis thaliana acyl-ACP
thioesterase gene. It is notable that changes in transgenic wheats
mimic those seen in plants grown under 'Greenhouse' conditions.
16 Differential effects of n-3 polyunsaturated fatty acids on
tendon versus cartilage metabolism
S.G. Rees, C.L. Curtis, B. Caterson, J.L. Harwood
Connective Tissue Biology Labs, Cardiff University,
CFlO 3US.
Previous studies have demonstrated that exposure of normal bovine
and human osteoarthritic cartilage to n-3 polyunsaturated fatty acids
(PUFAs), but not other classes of fatty acids, can modulate the
expression and activity of degradative and inflammatory factors that
are responsible for cartilage destruction. In these studies, supplementation of cartilage explant cultures with n-3 PUFAs resulted in
the dose-dependent reduction in aggrecanase and collagenase proteolytic activity. In addition, the expression of m R N A for the
inflammatory mediators cyclooxygenase-2,5-lipoxygenase,5lipoxygenase-activating protein, tumour necrosis factor- (Y and
interleukin-la and p was also abolished. The present work examines
the effect of n-3 PUFA supplementation o n tendon metabolism.
Importantly, within this musculoskeletal tissue, aggrecanases are
constitutively active and appear to be involved in normal, everyday
turnover of aggrecan, in contrast to articular cartilage. Exposure of
bovine tendon explant cultures to either n-3 o r n-6 PUFAs had no
effect o n the mRNA expression o r activity of aggrecanases;
similarly, expression of the inflammatory mediators was also
unaffected. These data demonstrate that the incorporation of n-3
PUFAs have a differential effect o n the regulatory mechanisms
which control gene expression within articular cartilage versus
tendon. Studies are currently underway to elucidate the precise
nature of these control mechanisms.
A I2I
17 Effect of AMPK activation o n fatty acid metabolism in
epithelia
C. Ghioni, K.J. Treharne, A. Mehta, R.E. Olver, S.C. Land,
R. Muimo
TICH, University of Dundee, Ninewells Hospital, Dundee,
DD19SY
AMP-activated protein kinase (AMPK) regulates mammalian lipid
metabolism by phosphorylating key enzymes including acetyl-CoA
carboxylase, 3-hydroxy-3-methylglutaryl-CoA-reductase,
lipase and
sn-glycerol-3-phosphate acyltransferase. We have shown the
presence of AMPK at the apical membrane of airway epithelium and
a human bronchial epithelial cell line (HBE). However, the function
of AMPK in airway epithelia is not well characterised.
Here we show that HBE cells treated with the AMPK activator, 5amino-4-imidazole carboxamine riboside (AICAR, 0.6 mM), display
a reduced rate of oxidation (28% less) of 14C-stearic acid (18:0), as
measured by I4C-CO2 release. AICAR also induces HBE cells to
convert more 14C-stearic acid into monounsaturated fatty acids
(oleic acid) (22% vs. 15%) but does not affect radioactivity incorporation into total and individual lipid classes. Following
supplementation with 20 p M linoleic acid (18:2w6), AICAR treated
HBE cells generate more arachidonic acid, as well as longer chain
saturated and monounsaturated fatty acids . Thus AICAR increases
the elongation/desaturation of w6 PUFA in HBE cells.
O u r results suggest that in airway epithelia the regulation of fatty
acid metabolism differs from liver and muscle and that AMPK may
play a role in the regulation of desaturases.
Financial Support: Wellcome program grant, C F Trust, Anon. Trust.
18 Dipalmitoylphosphatidylcholine regulates PGEZ release in
monocytes via effects o n PPAR-gamma.
T.T. Lin, A. Thomas, M. Ahluwalia, S.K. Jackson, A. Tonks,
A. Price, K.P. Jones, K. Morris.
School of Biomedical Sciences, UWIC, Western Avenue
Cardiff; CFli 2YB and Departments of Medical Microbiology
and Haematology, University of Wales College of Medicine,
Heath Park, Cardiff CF14 4XN
The disaturated species of phosphatidylcholine (1,2Dipalmitoylphosphatidylcholine;DPPC), is a major component of
lung surfactant, with a crucial role in preventing lung collapse at the
end of expiration. Increasingly, an immunoregulatory role for
D P P C has been reported, including its ability to regulate inflammatory cytokine release in monocytes and macrophages. In this study
we investigated the ability of D P P C to modulate the production of
the regulator of inflammatory cytokine release, prostaglandin E2
(PGE2) from a human monocyte cell line (MonoMac 6 ) . DPPC, at a
concentration of 250micrograms/ml, was able to significantly
(p<O.Ol) increase the secretion of PGEZ in LPS-stimulated
MonoMac 6 cells. When D P P C was substituted by the polyunsaturated species 1 -palmitoyl,2-arachidonoyl PC, no significant increase
in PGE2 secretion was observed. Furthermore, incubation of
MonoMac 6 cells with D P P C directly down-regulated the
expression of the nuclear lipid receptor PPAR-gamma. This study
suggests that the anti-inflammatory properties of D P P C may be
mediated via its effects o n PPAR-gamma expression and subsequent
PGE2 production.
0 2002 Biochemical Society