Wheat gliadin induces apoptosis of intestinal cells via an autocrine mechanism involving Fas–Fas ligand pathway

FEBS Letters

Scazzocchio, Beatrice¹  Malorni, Walter²  Matarrese, Paola²  Giovannini, Claudio¹  Varı̀, Rosaria¹  D’Archivio, Massimo¹  De Vincenzi, Massimo¹  Straface, Elisabetta²  Masella, Roberta¹ 

[1] Department of Metabolism and Pathological Biochemistry, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;Department of Ultrastructures, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy

关键词: Gliadin-derived peptide;    Apoptosis;    CD95/Fas;    Caco-2;    CM-H2DCFDA;    5-chloromethyl-2′;    7′-dichloro-dihydrofluoresceindiacetate;    DEVD-CHO;    Asp-Glu-Val-Asp-aldehyde;    DHR 123;    dihydrorhodamine 123;    DMEM;    Dulbecco's modified Eagle's medium;    HE;    hydroetidine;    Gl–PT;    gliadin–peptic-tryptic;    IETD-CHO;    Ile-Glu-Thr-Asp-aldehyde;    LEHD-CHO;    Leu-Glu-His-Asp-aldehyde;    PI;    propidium iodide;    PT;    peptic-tryptic;    ROS;    reactive oxygen species;   

DOI  :  10.1016/S0014-5793(03)00236-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Wheat gliadin and other cereal prolamins have been said to be involved in the pathogenic damage of the small intestine in celiac disease via the apoptosis of epithelial cells. In the present work we investigated the mechanisms underlying the pro-apoptotic activity exerted by gliadin-derived peptides in Caco-2 intestinal cells, a cell line which retains many morphological and enzymatic features typical of normal human enterocytes. We found that digested peptides from wheat gliadins (i) induce apoptosis by the CD95/Fas apoptotic pathway, (ii) induce increased Fas and FasL mRNA levels, (iii) determine increased FasL release in the medium, and (iv) that gliadin digest-induced apoptosis can be blocked by Fas cascade blocking agents, i.e. targeted neutralizing antibodies. This favors the hypothesis that gliadin could activate an autocrine/paracrine Fas-mediated cell death pathway. Finally, we found that (v) a small peptide (1157 Da) from durum wheat, previously proposed for clinical practice, exerted a powerful protective activity against gliadin digest cytotoxicity.

【 授权许可】

Unknown