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1 Departments of Nutrition and Medicine, University of Toronto, Toronto, Ontario M5S 1A8; and 2 Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1
Previous studies showed that weight-gaining rats
had greater retention and reduced turnover of
125I-labeled tumor necrosis factor
(TNF)-
in the circulation compared with weight-losing
animals. We therefore tested the hypothesis that protein-energy
restriction with weight loss reduces the levels of soluble TNF-
receptor (sTNFR) and membrane TNFR (mTNFR) and the cellular expression
of TNF-
mRNA. Twenty-six male rats weighing 200-220 g were fed
a liquid formula diet for 10 days and divided equally into
weight-gaining rats meeting all nutritional requirements (WG rats) and
weight-losing rats with protein-energy restriction (WL rats).
125I-TNF-
binding was
demonstrated in plasma and plasma membrane to proteins of molecular
masses of 92 and 243 kDa, a finding identical to that seen with
purified human p55. Excess unlabeled TNF-
displaced the binding
showing its specificity. The degree of binding to plasma protein and
liver plasma membrane was markedly reduced in WL rats. Northern
analysis showed that the expression of p55 mRNA was increased in the
lungs and reduced in kidneys of WL compared with WG rats. The
expression of p75 mRNA was not influenced by the nutritional status. We
conclude that levels of sTNFR and mTNFR were reduced in WL rats.
Reduced sTNFR and liver mTNFR are not due to a reduction in the
expression of either p55 or p75 mRNA in WL rats. Reduced mTNFR,
together with reduced shedding of soluble receptors, may have a
protective role in WL rats.
electrophoresis; Northern blot; probes; plasma membranes
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