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Differential intestinal mucosal protein expression in hypercholesterolemic mice fed a phytosterol‐enriched diet
Author(s) -
CalpeBerdiel Laura,
EscolàGil Joan Carles,
Julve Josep,
ZapicoMuñiz Edgar,
Canals Francesc,
BlancoVaca Francisco
Publication year - 2007
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200600792
Subject(s) - phytosterol , food science , biology , protein expression , chemistry , biochemistry , gene
The molecular mechanisms involved in the phytosterol‐induced decrease in intestinal cholesterol absorption remain unclear. Further, other biological properties such as immunomodulatory activity and protection against cancer have also been ascribed to these plant compounds. To gain insight into the mechanisms underlying phytosterol actions, we conducted a proteomic study in the intestinal mucosa of phytosterol‐fed apolipoprotein E‐deficient hypercholesterolemic (apoE−/−) mice. With respect to control‐fed apoE−/− mice, nine differentially expressed proteins were identified in whole‐enterocyte homogenates using 2‐D DIGE and MALDI‐TOF MS. These proteins are involved in plasma membrane stabilization, cytoskeleton assembly network, and cholesterol metabolism. Four of these proteins were selected for further study since they showed the highest abundance change or had a potential functional relationship with known effects of phytosterols. Annexin A2 (ANXA2) and β‐actin decrease and annexin A4 (ANXA4) and annexin A5 (ANXA5) increase were confirmed by Western blot analysis. Intestinal gene expression of ANXA2 and A5 and β‐actin was reduced, whereas that of ANXA4 was unchanged. The main results were retested in normocholesterolemic C57BL/6J mice. ANXA4 and ANXA5 protein upregulation and ANXA2 and β‐actin downregulation were reproduced in these animals. However, no changes in gene expression were found in C57BL/6J mice in either of the four proteins selected. ANXA2, A4, and A5 and β‐actin are proteins of special interest given their pleiotropic functions that include cholesterol‐ester transport from caveolae, apoptosis, and anti‐inflammatory properties. Therefore, the protein expression changes identified in this study might be involved in the biological effects of phytosterols.