K. Wingler et al., Gastrointestinal glutathione peroxidase prevents transport of lipid hydroperoxides in CaCo-2 cells, GASTROENTY, 119(2), 2000, pp. 420-430
Background ge Aims: Gastrointestinal glutathione peroxidase (Gl-GPx), 1 of
the 4 types of selenium-dependent glutathione peroxidases, is expressed exc
lusively in the gastrointestinal system and has therefore been suggested to
function as a barrier against the absorption of dietary hydroperoxides. Me
thods: The selenium-dependent expression of Gl-GPx and cytosolic GPx (cGPx)
was analyzed by Western blotting. Transport of 13-hydroperoxy octadecadien
oic acid (13-HPODE) was investigated in a CaCo-2 cell monolayer modulated i
n Gl-GPx and cGPx by selenium restriction or repletion. Localization of Gl-
GPx in rat intestine was visualized by immunohistochemistry, Results: Low b
ut significant Gl-GPx levels were detected in selenium-deficient CaCo-2 cel
ls and in the gastrointestinal tract of selenium-deficient rats, whereas cG
Px was completely absent. Selenium supplementation of CaCo-2 cells resulted
in a 5-fold increase of Gl-GPx protein, whereas total GPx activity increas
ed by a factor of 13, with most of the GPx activity under selenium-adequate
conditions being cGPx. Irrespective of the selenium status, 13-HPODE did n
ot reach the basolateral side of an intact CaCo-2 cell monolayer, Depending
on the selenium status, hydroperoxides damaged the monolayer as evidenced
by toss of transepithelial resistance and paracellular diffusion of lucifer
yellow, Only under these conditions was unmetabolized 13-HPODE detectable
at the basolateral side. Conclusions: Low Gl-GPx levels, as present in sele
nium deficiency, suffice to prevent transport of 13-HPODE. Gl-GPx may thus
function as a barrier against hydroperoxide absorption, cGPx contributes to
balance major oxidative challenge.